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Research Article

Recent Progress in the Pathogenesis of Nephrotic Proteinuria

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Pages 139-220 | Published online: 10 Oct 2008

REFERENCES

  • Kestila M, Lenkkeri U, Mannikko M, Lameerin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan C E, Peltonen L, Holmberg C, Olsen A, Tryggvason K. Positionally cloned gene for a novel glomerular protein – nephrin – is mutated in congenital nephrotic syndrome. Mol Cell 1998; 1: 575–582
  • Orth S R, Ritz E. The nephrotic syndrome. N Engl J Med 1998; 338: 1202–1211
  • Tesar V, Zima T, Kalousova M. Pathobiochemistry of nephrotic syndrome. Adv Clin Biochem 2002; 37: 173–218
  • Smithies O. Why the kidney glomerulus does not clog: a gel permeation/diffusion hypothesis of renal function. Proc Natl Acad Sci USA 2003; 100: 4108–4113
  • Deen W M. What determines glomerular capillary permeability?. J Clin Invest 2004; 114: 1412–1414
  • Guasch A, Myers B D. Determinants of glomerular hypofiltration in nephrotic patients with minimal change nephropathy. J Am Soc Nephrol 1994; 4: 1571–1581
  • D'Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int 2003; 63: 809–825
  • Van d en, Born J, van den Heuvel L P, Bakker M A, Veerkamp J H, Assmann K J, Berden J H. A monoclonal antibody against GBM heparan sulfate induces an acute selectve proteinuria in rats. Kidney Int 1992; 41: 115–123
  • Kawachi H, Kurihara H, Topham P S, Brown D, Shia M A, Orikasa M, Shimizu F, Salant D J. Slit diaphragm-reactive nephritogenic MAb 5-1-6 alters expression of ZO-1 in rat podocytes. Am J Physiol 1997; 273: F984–F993
  • Caulfield J P, Farquhar M P. The permeability of glomerular capillaries to graded dextrans: identification of the basement membrane as the primary filtration barrier. J Cell Biol 1974; 63: 883–903
  • Kanwar Y S, Liu Z Z, Kashihara N, Wallner E I. Current status of the structural and functional basis of glomerular filtration and proteinuria. Semin Nephrol 1991; 11: 390–413
  • Rossi M, Morita H, Sormunen R, Airenne S, Kreivi M, Wang L, Fukai N, Olsen B R, Tryggvason K, Soininen R. Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J 2003; 22: 236–245
  • Jarad G, Cunningham J, Shaw A S, Miner J H. Proteinuria precedes podocyte abnormalities in Lamb2−/− mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 2006; 116: 2272–2279
  • Farquhar M G. The glomerular basement membrane: not gone, just forgotten. J Clin Invest 2006; 116: 2090–2093
  • Yoshioka N, Ito H, Akamatsu R, Hazikano H, Okada S, Matsuo T. Glomerular podocyte vacuolation in focal segmental glomerulosclerosis. Arch Pathol Lab Med 1986; 110: 394–398
  • Eyre J, Ioannou K, Grubb B D, Saleem M A, Mathieson P W, Brunskill N J, Christensen E I, Topham P S. Statin-sensitive endocytosis of albumin by glomerular podocytes. Am J Physiol Renal Physiol 2007; 292: F674–F681
  • Bulger R E, Eknoyan G, Purcell D J, Dobyan D C. Endothelial characteristic of glomerular capillaries in normal, mercuric-chloride-induced, and gentamicin-induced acute renal failure in the rat. J Clin Invest 1983; 72: 128–141
  • Sawada H, Stukenbrok H, Kerjaschki D, Farquhar M G. Epithelial polyanion (podocalyxin) is found on the sides but not the soles of the foot processes of the glomerular epithelium. Am J Pathol 1986; 125: 309–318
  • Eremina V, Quaggin S E. The role of VEGF-A in glomerular development and function. Curr Opin Nephrol Hypertens 2004; 13: 9–15
  • Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, Gerber H P, Kikkawa Y, Miner J H, Quaggin S E. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 2003; 111: 707–716
  • Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, Kalluri R. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 2003; 278: 12605–12608
  • Kalluri R. Proteinuria with and without renal glomerular podocyte effacement. J Am Soc Nephrol 2006; 17: 2383–2389
  • Hudson B G, Reeder S T, Tryggvason K. Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem 1993; 268: 26033–26036
  • Tryggvason K, Wartiovara J. Molecular basis of glomerular permselectivity. Curr Opin Nephrol Hypertens 2001; 10: 543–549
  • Badens C, Praga M, Tazón B, Heidet L, Arrondel C, Armengol A, Andrés A, Morales E, Camacho A, Lens X, Dávila S, Mila M, Antignac C, Darnell A, Torra R. Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 2002; 13: 1248–1254
  • Noakes P G, Miner J H, Gautam M, Cunningham J M, Sanes J R, Merlie J P. The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet 1995; 10: 400–406
  • Dandapani S V, Pollak M R. The glomerular filter: biologic and genetic complexity. Kidney Int 2006; 70: 980–982
  • Zenker M, Aigner T, Wendler O, Tralau T, Muntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wuhl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dotsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann L M, Reis A. Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 2004; 13: 2625–2632
  • Hasselbacher K, Wiggins R C, Matejas V, Hinkes B G, Mucha B, Hoskins B E, Ozaltin F, Nurnberg G, Becker C, Hangan D, Pohl M, Kuwertz-Broking E, Griebel M, Schumacher V, Royer-Pokora B, Bakkaloglu A, Nurnberg P, Zenker M, Hildebrandt F. Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int 2006; 70: 1008–1012
  • Kanwar Y S, Farquhar M G. Presence of heparan sulfate in the glomerular basement membrane. Proc Natl Acad Sci USA 1979; 76: 1303–1307
  • Hassel J R, Robey P G, Barrach H J, Wilczek J, Rennard S I, Martin G R. Isolation of a heparan sulfate-containing proteoglycan from basement membrane. Proc Natl Acad Sci USA 1980; 77: 4494–4498
  • Groffen A J, Ruegg M A, Dijkman H, van de Velden T J, Buskens C A, van den Born J, Assmann K J, Monnens L A, Veerkamp J H, van den Heuvel L P. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem 1998; 46: 19–27
  • Rops A L, van der Vlag J, Lensen J E, Wijnhoven T J, van den Heuvel L P, van Kuppevelt T H, Berden J H. Heparan sulfate proteglycans in glomerular inflammation. Kidney Int 2004; 65: 768–785
  • Kanwar Y S, Linker A, Farquhar M G. Increased permeability of the glomerular basement membrane in aminonucleoside nephrosis. J Cell Biol 1980; 86: 688–693
  • Caulfield J P, Farquhar M G. Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 1978; 39: 505–512
  • Harvey S J, Miner J. Podocyte-derive agrin is responsible for glomerular basement membrane anionic charge. J Am Soc Nephrol 2005; 16: 1A, abstract
  • Morita H, Yoshimura A, Inui K, Ideura T, Watanabe H, Wang L, Soininen R, Tryggvason K. Heparan sulfate of perlecan is involved in glomerular filtration. J Am Soc Nephrol 2005; 16: 1703–1710
  • Russo L M, Bakris G L, Comper W D. Renal handling of albumin: a critical review of basic concepts and perspective. Am J Kidney Dis 2002; 39: 899–919
  • Pavenstädt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev 2003; 83: 253–307
  • Marshall C B, Shankland S J. Cell cycle and glomerular disease: a minireview. Nephron Exp Nephrol 2006; 102: e39–e48
  • Kriz W, Hackenthal E, Nobiling R, Sakai T, Elger M, Hahnel B. A role for podocytes to counteract capillary wall distention. Kidney Int 1994; 45: 369–376
  • Shankland S J. The podocyte's response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 2006; 69: 2131–2147
  • Barisoni L, Kriz W, Mundel P, D'Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999; 10: 51–61
  • Schmieder S, Nagai M, Orlando R A, Takeda T, Farquhar M G. Podocalyxin activates RhoA and induces actin reorganization through NHERF1 and ezrin in MCDK cells. J Am Soc Nephrol 2004; 15: 2289–2298
  • Orlando R A, Takeda T, Zak B, Schmieder S, Benoit V M, McQuistan T, Furthmayr H, Farquhar M G. The glomerular epithelial cell anti-adhesin podocalyxin associates with the actin cytoskeleton through interactions with ezrin. J Am Soc Nephrol 2001; 12: 1589–1598
  • Takeda T, McQuistan T, Orlando R A, Farquhar M G. Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin Invest 2001; 108: 289–301
  • Breiteneder-Geleff S, Matsui K, Soleiman A, Meraner P, Poczewski H, Kalt R, Schaffner G, Kerjaschki D. Podoplanin, a novel 43-kd membrane protein of glomerular epithelial cells, is downregulated in puromycin nephrosis. Am J Pathol 1997; 151: 1141–1152
  • Farquhar M, Saito A, Kerjaschki D, Orlando R A. The Heymann nephritis antigenic complex: Megalin (gp330) and RAP. J Am Soc Nephrol 1995; 6: 35–47
  • Kriz W, Elger M, Mundel P, Lemley K V. Structure-stabilizing forces in the glomerular tuft. J Am Soc Nephrol 1995; 5: 1731–1739
  • Endlich N, Kress K R, Reiser J, Uttenweiler D, Kriz W, Mundel P, Endlich K. Podocytes respond to mechanical stress in vitro. J Am Soc Nephrol 2001; 12: 413–422
  • Endlich N, Endlich K. Stretch, tension and adhesion – adaptive mechanisms of the actin cytoskeleton in podocytes. Eur J Cell Biol 2006; 85: 229–234
  • Morton M J, Hutchinson K, Mathieson P W, Witherden I R, Saleem M A, Hunter M. Human podocytes possess a stretch-sensitive, Ca2 +-activated K+ channel: potential implications for the control of glomerular filtration. J Am Soc Nephrol 2004; 15: 2981–2987
  • Reiser J, Polu K R, Moller C C, Kenlan P, Altintas M M, Wei C, Faul C, Herbert S, Villegas I, Avila-Casado C, McGee M, Sugimoto H, Brown D, Kalluri R, Mundel P, Smith P L, Clapham D E, Pollak M R. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 2005; 37: 739–744
  • Winn M P, Conlon P J, Lynn K L, Farrington M K, Creazzo T, Hawkins A F, Daskalakis N, Kwan S Y, Ebersviller S, Burchette J L, Pericak-Vance M A, Howell D N, Vance J M, Resonberg P B. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 2005; 308: 1801–1804
  • Huber T B, Gloy J, Henger A, Schollmeyer P, Greger R, Mundel P, Pavenstadt H. Catecholamines modulate podocyte function. J AmSoc Nephrol 1998; 9: 335–345
  • Sharma R, Lovell H B, Wiegmann T B, Savin V J. Vasoactive substances induce cytoskeletal changes in cultured rat glomerular epithelial cells. J Am Soc Nephrol 1992; 3: 1131–1138
  • Pavenstädt H. The charge for going by foot: modifying the surface of podocytes. Exp Nephrol 1998; 6: 98–103
  • Rodriguez O C, Schaefer A W, Mandato C A, Forscher P, Bement W M, Waterman-Storer C M. Conserved microtubule-actin interactions in cell movement and morphogenesis. Nature Cell Biol 2003; 5: 599–609
  • Gao S Y, Li C Y, Chen J, Pan L, Saito S, Terashita T, Saito K, Miyawaki K, Shigemoto K, Mominoki K, Matsuda S, Kobayashi N. Rho-ROCK signal pathway regulates microtubule-based process formation of cultured podocytes – inhibition of ROCK promoted process elongation. Nephron Exp Nephrol 2004; 97: e49–e61
  • Cybulsky A V, Carbonetto S, Huang Q, McTavish A J, Cyr M D. Adhesion of rat glomerular epithelial cells to extracellular matrices. Role of β 1 integrins. Kidney Int 1992; 42: 1099–1106
  • Kojima K, Davidovits A, Poczewski H, Langer B, Uchida S, Nagy-Bojarski K, Hovorka A, Sedivy R, Kerjaschki D. Podocyte flattening and disorder of glomerular basement membrane are associated with splitting of dystroglycan-matrix interaction. J Am Soc Nephrol 2004; 15: 2079–2089
  • Teixeira V, Blattner S M, Li M, Anders H J, Cohen C D, Edenhofer I, Calvaresi N, Merkle M, Rastaldi M P, Kretzler M. Functional consequences of integrin-linked kinase activation in podocyte damage. Kidney Int 2005; 67: 514–523
  • Critchley D R. Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion. Biochem Soc Trans 2004; 32: 831–836
  • Kreidberg J A. Podocyte differentiation and glomerulogenesis. J Am Soc Nephrol 2003; 14: 806–814
  • Usui J, Kurihara H, Shu Y, Tomari S, Kanemoto K, Koyama A, Sakai T, Takahashi T, Nagata M. Localization of intercellular adherens junction protein p120 catenin during podocyte differentiation. Anat Embryol 2003; 206: 175–184
  • Takeda T, Go W Y, Orlando R A, Farquhar M G. Expression of podocalyxin inhibits cell-cell adhesion and modifies junctional properties in Madin-Darby canine kidney cells. Mol Biol Cell 2000; 11: 3219–3232
  • Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med 2006; 354: 1387–1401
  • Moeller M J. Dynamics at the slit diaphragm – is nephrin actin?. Nephrol Dial Transplant 2007; 22: 37–39
  • Andrews P M. Investigations of cytoplasmic contractile and cytoskeletal elements in the kidney glomerulus. Kidney Int 1981; 20: 549–562
  • Shirato I, Sakai T, Kimura K, Tomino Z, Kriz W. Cytoskeletal changes in podocytes associated with foot process effacement in Masugi nephritis. Am J Pathol 1996; 148: 1283–1296
  • Reiser J, Oh J, Shirato I, Asanuma K, Hug A, Mundel T M, Honey K, Ishidoh K, Kominami E, Kreidberg J A, Tomino Y, Mundel P. Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and α 3 integrin. J Biol Chem 2004; 279: 34827–34832
  • Kerjaschki D. Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis. J Clin Invest 2001; 108: 1583–1587
  • Karumanchi S A, Maynard S E, Stillman I E, Epstein F H, Sukhatme V P. Preeclampsia: a renal perspective. Kidney Int 2005; 67: 2101–2113
  • Van d en, Berg J G, Weerman M A, Assmann K J, Weening J J, Florquin S. Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int 2004; 66: 1901–1906
  • Garovic V C, Wagner S J, Petrovic L M, Gray C E, Hall P, Sugimoto H, Kalluri R, Grande J P. Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant 2007; 22: 1136–1143
  • Yu Y, Leng C G, Kato Y, Ohno S. Ultrastructural study of glomerular capillary loops at different perfusion pressures as revealed by quick-freezing, freeze-substitution and conventional fixation methods. Nephron 1997; 76: 452–459
  • Rodewald R, Karnovsky M J. Porous substructure of the glomerular slit diaphragm in the rat and mouse. J Cell Biol 1974; 60: 621–624
  • Kurihara H, Anderson J M, Farquhar M G. Diversity among tight junctions in rat kidney: Glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1. Proc Natl Acad Sci USA 1992; 89: 7075–7079
  • Reiser J, Kriz W, Kretzler M, Mundel P. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol 2000; 11: 1–8
  • Yaoita E, Yao J, Yoshida Y, Morioka T, Nameta M, Takata T, Kamiie J, Fujinaka H, Oite T, Yamamoto T. Up-regulation of connexin43 in glomerular podocytes in response to injury. Am J Pathol 2002; 161: 1597–1606
  • Saez J C, Berthoud V M, Branes M C, Martinez A D, Beyer E C. Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 2003; 83: 1359–1400
  • Silverstein D M, Urban M, Gao Y, Mattoo T K, Spray D C, Rozental R. Renal morphology in connexin43 knockout mice. Pediatr Nephrol 2001; 16: 467–471
  • Sawai K, Mukoyama M, Mori K, Yokoi H, Koshikawa M, Yoshioka T, Takeda R, Sugawara A, Kuwahara T, Saleem M A, Ogawa O, Nakao K. Redistribution of connexin43 expression in glomerular podocytes predicts poor renal prognosis in patients with type 2 diabetes and overt nephropathy. Nephrol Dial Transplant 2006; 21: 2472–2477
  • Orikasa M, Matsui K, Oite T, Shimizu F. Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody. J Immunol 1988; 141: 807–814
  • Kawachi H, Abrahamson D R, John P L, Goldstein D J, Shia M A, Matsui K, Shimizu F, Salant D J. Developmental expression of the nephritogenic antigen of monoclonal antibody 5-1-6. Am J Pathol 1995; 147: 823–833
  • Topham P S, Kawachi H, Haydar S A, Chugh S, Addona T A, Charron K B, Holzman L B, Shia M, Shimizu F, Salant D J. Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin. J Clin Invest 1999; 104: 1559–1566
  • Tryggvason K. Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm. J Am Soc Nephrol 1999; 10: 2440–2445
  • Tryggvason K, Ruotsalainen V, Wartiovaara J. Discovery of the congenital nephrotic syndrome gene discloses the structure of the mysterious molecular sieve of the kidney. Int J Dev Biol 1999; 43: 445–451
  • Putaala H, Soininen R, Klipelainen P, Wartiovaara J, Tryggvason K. The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet 2001; 10: 1–8
  • Wang S X, Ahola H, Palmen T, Solin M L, Luimula P, Holthofer H. Recurrence of nephrotic syndrome after transplantation in CNF is due to autoantibodies to nephrin. Exp Nephrol 2001; 9: 327–331
  • Wartiovaara J, Ofverstedt L G, Khoshnoodi J, Zhang J, Makela E, Sandin S, Ruotsalainen V, Cheng R H, Jalanko H, Skoglund U, Tryggvason K. Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. J Clin Invest 2004; 114: 1475–1483
  • Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi P G, Reponen P, Tryggvason K, Camussi G. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 2001; 158: 1723–1731
  • Patari A, Forsblom C, Havana M, Taipale H, Groop P H, Holthofer H. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes 2003; 52: 2969–2974
  • Han Y P, Tuan T L, Wu H, Hughes M, Garner W L. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci 2001; 114: 131–139
  • Takano Y, Yamauchi K, Hiramatsu N, Kasai A, Hayakawa K, Yokouchi M, Yao J, Kitamura M. Recovery and maintenance of nephrin expression in cultured podocytes and identification of HGF as a repressor of nephrin. Am J Physiol Renal Physiol 2007; 292: F1573–F1582
  • Takano Y, Yamauchi K, Hayakawa K, Hiramatsu N, Kasai A, Okamura M, Yokouchi M, Shitamura A, Yao J, Kitamura M. Transcriptional suppression of nephrin in podocytes by macrophages: roles of inflammatory cytokines and involvement of the PI3K/Akt pathway. FEBS Lett 2007; 581: 421–426
  • Donoviel D B, Freed D D, Vogel H, Potter D G, Hawkins E, Barrish J P, Mathur B N, Turner C A, Geske R, Montgomery C A, Starbuck M, Brandt M, Gupta A, Ramirez-Solis R, Zambrowicz B P, Powell D R. Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to nephrin. Mol Cell Biol 2001; 21: 4829–4836
  • Gerke P, Sellin L, Kretz O. NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases. J Am Soc Nephrol 2005; 16: 1693–1702
  • Michaud J L, Kennedy C R. The podocyte in health and disease: insights from the mouse. Clin Sci 2007; 112: 325–335
  • Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler M D, Niaudet P, Antignac C. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000; 24: 349–354
  • Schwarz K, Simons M, Reiser J, Saleem M A, Faul C, Kriz W, Shaw A S, Holzman L B, Mundel P. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest 2001; 108: 1621–1629
  • Harder T. Lipid raft domains and protein networks in T-cell receptor signal transduction. Curr Opin Immunol 2004; 16: 353–359
  • Luimula P, Sandstrom N, Novikov D, Holthofer H. Podocytes-associated molecules in puromycin aminonucleoside nephrosis of the rat. Lab Invest 2002; 82: 713–718
  • Miner J H, Morello R, Andrews K L, Li C, Antignac C, Shaw A S, Lee B. Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J Clin Invest 2002; 109: 1065–1072
  • Dustin M L, Olszowy M W, Holdorf A D, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe P A, Allen P M, Shaw A S. A novel adaptor protein orchestrates receptor patterning and cytoskeleletal polarity in T-cell contacts. Cell 1998; 94: 667–677
  • Shih N Y, Li J, Karpitskij V, Nguyen A, Dustin M L, Kanagawa O, Miner J H, Shaw A S. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 1999; 286: 312–315
  • Tossidou I, Kardinal C, Peters I, Kriz W, Shaw A, Dikic I, Tkachuk S, Dumler I, Haller H, Schiffer M. CD2AP/CIN85 balance determines RTK-signaling response in podocytes. J Biol Chem 2007; 282: 7457–7464
  • Benzing T. Signaling at the slit diaphragm. J Am Soc Nephrol 2004; 15: 1382–1391
  • Patrakka J, Xiao Z, Nukui M, Takemoto M, He L, Oddsson A, Perisic L, Kaukinen A, Al-Khalili A, Szigyarto C, Uhlén M, Jalanko H, Betsholtz C, Tryggvason K. Expression and subcellular distribution of novel glomerulus-associated proteins dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik. J Am Soc Nephrol 2007; 18: 689–697
  • Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi M P, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe A H, Kreidberg J A, Mundel P. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004; 113: 1390–1397
  • Lahdenpera J, Kilpelainen P, Liu X L, Pikkarainen T, Reponen P, Ruotsalainen V, Tryggvason K. Clustering-induced tyrosine phosphorylation of nephrin by src family kinases. Kidney Int 2003; 64: 404–413
  • Verma R, Wharram B, Kovari I, Kunkel R, Nihalani D, Wary K K, Wiggins R C, Killen P, Holzman L B. Fyn binds to and phosphorylates the kidney slit diaphragm component nephrin. J Biol Chem 2003; 278: 20716–20723
  • Wang S X, Mene P, Holthofer H. Nephrin mRNA regulation by protein kinase C. J Nephrol 2001; 14: 98–103
  • Liu X L, Kilpeläinen P, Hellman U, Sun Y, Wartiovaara J, Morgunova E, Pikkarainen T, Yan K, Jonsson A P, Tryggvason K. Characterization of the interactions of the nephrin intracellular domain. Evidence that the scaffolding protein IQGAP1 associates with nephrin. FEBS J 2005; 272: 228–243
  • Meier M, Menne J, Park J K, Holtz M, Gueler F, Kirsch T, Schiffer M, Mengel M, Lindschau C, Leitges M, Haller H. Deletion of protein kinase C-ε signaling pathway induces glomerulosclerosis and tubulointerstitial fibrosis in vivo. J Am Soc Nephrol 2007; 18: 1190–1198
  • Verma R, Kovari I, Soofi A, Nihalani D, Patrie K, Holzman L B. Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization. J Clin Invest 2006; 116: 1346–1359
  • Yu C C, Yen T S, Lowell C A, DeFranco A L. Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn. Curr Biol 2001; 11: 34–38
  • Huber T B, Simons M, Hartleben B, Sernetz L, Schmidts M, Gundlach E, Saleem M A, Walz G, Benzing T. Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Hum Mol Genet 2003; 12: 3397–3405
  • Li H, Lemay S, Aoudjit L, Kawachi H, Takano T. Src-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin. J Am Soc Nephrol 2004; 15: 3006–3015
  • Quack I, Rump L C, Gerke P, Walther I, Vinke T, Vonend O, Grunwald T, Sellin L. β -arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity. Proc Natl Acad Sci USA 2006; 103: 14110–14115
  • Huber T B, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, Egger L, Lecha R L, Borner C, Pavenstadt H, Shaw A S, Walz G, Benzing T. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 2003; 23: 4917–4928
  • Foster R R, Saleem M A, Mathieson P W, Bates D O, Harper S J. Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes. Am J Physiol Renal Physiol 2005; 288: F48–F57
  • Kim Y H, Goyal M, Kurnit D, Wharram B, Wiggins J, Holzman L, Kershaw D, Wiggins R. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int 2001; 60: 957–968
  • Tryggvason K, Pikkarainen T, Patrakka J. Nck links nephrin to actin in kidney podocytes. Cell 2006; 125: 221–224
  • Buday L, Wunderlich L, Tamás P. The Nck family of adapter proteins: regulators of actin cytoskeleton. Cell Signal 2002; 14: 723–731
  • Jones N, Blasutig I M, Eremina V, Ruston J M, Bladt F, Li H, Huang H, Larose L, Li S S, Takano T, Quaggin S E, Pawson T. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature 2006; 440: 818–823
  • Huber T B, Schmidts M, Gerke P, Schermer B, Zahn A, Hartleben B, Sellin L, Walz G, Benzing T. The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1. J Biol Chem 2003; 278: 13417–13421
  • Lehtonen S, Lehtonen E, Kudlicka K, Holthofer H, Farquhar M G. Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. Am J Pathol 2004; 165: 923–936
  • Lehtonen S, Ryan J J, Kudlicka K, Iino N, Zhou H, Farquhar M G. Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrin, and alpha-actinin are components of the nephrin multiprotein complex. Proc Natl Acad Sci USA 2005; 102: 9814–9819
  • Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature 2002; 420: 629–635
  • Noritake J, Watanabe T, Sato K, Wang S, Kaibuchi K. IQGAP1: a key regulator of adhesion and migration. J Cell Sci 2005; 118: 2085–2092
  • Ho Y D, Joyal J L, Li Z, Sacks D B. IQGAP1 integrates Ca2+/calmodulin and Cdc42 signaling. J Biol Chem 1999; 274: 464–470
  • Li S, Wang Q, Chakladar A, Bronson R T, Bernards A. Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1. Mol Cell Biol 2000; 20: 697–701
  • Hirabayashi S, Mori H, Kansaku A, Kurihara H, Sakai T, Shimizu F, Kawachi H, Hata Y. MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin. Lab Invest 2005; 85: 1528–1543
  • Inoue T, Yaoita E, Kurihara H, Shimizu F, Sakai T, Kobayashi T, Ohshiro K, Kawachi H, Okada H, Suzuki H, Kihara I, Yamamoto T. FAT is a component of glomerular slit diaphragms. Kidney Int 2001; 59: 1003–1012
  • Moeller M J, Soofi A, Braun G S, Li X, Watzl C, Kriz W, Holzman L B. Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization. EMBO J 2004; 23: 3769–3779
  • Tanoue T, Takeichi M. New insights into Fat cadherins. J Cell Sci 2005; 118: 2347–2353
  • Ciani L, Patel A, Allen N D, French-Constant C. Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype. Mol Cell Biol 2003; 23: 3575–3582
  • Sun Y P, Björklund M, Koivunen R. Screening of a phage library with human nephrin reveals MEGF1/Fat2 as a novel component of the podocyte slit diaphragm. J Am Soc Nephrol 2005; 16: 108A, abstract
  • Quaggin S E. Transcriptional regulation of podocyte specification and differentiation. Microsc Res Tech 2002; 57: 208–211
  • Wagner K D, Wagner N, Schedi A. The complex life of WT1. J Cell Sci 2003; 116: 1653–1658
  • Yang Y, Jeanpierre C, Dressler G R, Lacoste M, Niaudet P, Gubler M C. WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. Am J Pathol 1999; 154: 181–192
  • Ohtaka A, Ootaka T, Sato H, Soma J, Sato T, Saito T, Ito S. Significance of early phenotypic change of glomerular podocytes detected by Pax2 in primary focal segmental glomerulosclerosis. Am J Kidney Dis 2002; 39: 475–485
  • Shankland S J, Eitner F, Hudkins K L, Goodpaster T, D'Agati V, Alpers C E. Differential expression of cyclin-dependent kinase inhibitors in human glomerular disease: role in podocyte proliferation and maturation. Kidney Int 2000; 58: 674–683
  • Shankland S J, Wolf G. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. Am J Physiol Renal Physiol 2000; 278: F515–F529
  • Barbaux S, Niaudet P, Gubler M C, Grunfeld J P, Jaubert F, Kuttenn F, Fekete C N, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 1997; 17: 467–470
  • Viney R L, Morrison A A, van den Heuvel L P, Ni L, Mathieson P W, Saleem M A, Ladomery M R. A proteomic investigation of glomerular podocytes from a Denys-Drash syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. Proteomics 2007; 7: 804–815
  • Dreyer S D, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, Johnson R L, Lee B. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet 1998; 19: 47–50
  • Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson R L, Antignac C, Witzgall R. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest 2002; 109: 1073–1082
  • Suleiman H, Heudobler D, Raschta A S, Zhao Y, Zhao Q, Hertting I, Vitzthum H, Moeller M J, Holzman L B, Rachel R, Johnson R, Westphal H, Rascie A, Witzgall R. The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev Biol 2007; 304: 701–712
  • Quaggin S E, Schwartz L, Cui S, Igarashi P, Deimling J, Post M, Rossant J. The basic-helix-loop-helix protein pod1 is critically important for kidney and lung organogenesis. Development 1999; 126: 5771–5783
  • Sadl V, Jin F, Yu J, Cui S, Holmyard D, Quaggin S, Barsh G, Cordes S. The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Dev Biol 2002; 249: 16–29
  • Liu G, Clement L C, Kanwar Y S, Avila-Casado C, Chugh S S. ZHX proteins regulate podocyte gene expression during the development of nephrotic syndrome. J Biol Chem 2006; 281: 39681–39692
  • Di Duca M, Oleggini R, Sanna-Cherchi S, Pasquali L, Di Donato A, Parodi S, Bertelli R, Caridi G, Frasca G, Cerullo G, Amoroso A, Schena F P, Scolari F, Ghiggeri G M. European IgA Nephropathy Consortium. Cis and trans regulatory elements in NPHS2 promoter: implications in proteinuria and progression of renal disease. Kidney Int 2006; 70: 1332–1341
  • Corre S, Galibert M D. Upstream stimulating factors: highly versatile stress-responsive transcription factors. Pigment Cell Res 2005; 18: 337–348
  • Ross M D, Martinka S, Mukherjee A, Sedor J R, Vinson C, Bruggeman L A. Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis. Dev Dyn 2006; 235: 3102–3109
  • Takemoto M, He L, Norlin J, Patrakka J, Xiao Z, Petrova T, Bondjers C, Asp J, Wallgard E, Sun Y, Samuelsson T, Mostad P, Lundin S, Miura C, Sado Y, Alitalo K, Quaggin S E, Tryggvason K, Betsholtz C. Large-scale identification of genes implicated in kidney glomerulus development and function. EMBO J 2006; 25: 1160–1174
  • Regele H M, Filipovic E, Langer B, Poczewski H, Kraxberger I, Bittner R E, Kerjaschki D. Glomerular expression of dystroglycans is reduced in minimal change nephrosis, but not in focal segmental glomerulosclerosis. J Am Soc Nephrol 2000; 11: 403–412
  • Raats C J, van den Born J, Bakker M A, Oppers-Walgreen B, Pisa B J, Dijkman H B, Assmann K J, Berden J H. Expression of agrin, dystroglycan, and utrophin in normal renal tissue and in experimental glomerulopathies. Am J Pathol 2000; 156: 1749–1765
  • Tisi D, Talts J F, Timpl R, Honenester E. Structure of the C-terminal laminin G-like domain pair of the laminin α 2 chain harbouring binding sites for α -dystroglycan and heparin. EMBO J 2000; 19: 1432–1440
  • Williamson R A, Henry M D, Daniels K J, Hrstka R F, Lee J C, Sunada Y, Ibraghimov-Beskrovnaya O, Campbell K P. Dystroglycan is essential for early embryonic development: disruption of Reicherts membrane in Dag1-null mice. Hum Mol Genet 1997; 6: 831–841
  • Good K S, O'Brien K, Schulman G, Kerjaschki D, Fogo A B. Unexplained nephrotic-range proteinuria in a 38-year old man: a case of “no change disease.”. Am J Kidney Dis 2004; 43: 933–938
  • Kretzler M, Teixeira V P, Unschuld P G, Cohen C D, Wanke R, Edenhofer I, Mundel P, Schlondorff D, Holthofer H. Integrin-linked kinase as a candidate downstream effector in proteinuria. FASEB J 2001; 15: 1843–1845
  • Adler S, Chen X. Anti-Fx1A antibody recognizes a β 1-integrin on glomerular epithelial cells and inhibits adhesion and growth. Am J Physiol 1992; 262: F770–F776
  • Kreidberg J A, Donovan M J, Goldstein S L, Rennke H, Shepherd K, Jones R C, Jaenisch R. Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development 1996; 122: 3537–3547
  • Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol 2001; 155: 505–510
  • Jung K Y, Chen K, Kretzler M, Wu C. TGF-β 1 regulates the PINCH-1-integrin-linked kinase-α -parvin complex in glomerular cells. J Am Soc Nephrol 2007; 18: 66–73
  • Novak A, Hsu S C, Leung-Hagesteijn C, Radeva G, Papkoff J, Montesano R, Roskelley C, Grosschedl R, Dedhar S. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways. Proc Natl Acad Sci USA 1998; 95: 4374–4379
  • El-Aouni C, Herbach N, Blattner S M, Henger A, Rastaldi M, Jarad G, Miner J H, Moeller M J, St-Arnaud R, Dedhar S, Holzman L B, Wanke R, Kretzler M. Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis. J Am Soc Nephrol 2006; 17: 1334–1344
  • Dai C, Stolz D B, Bastacky S I, St.-Arnaud R, Wu C, Dedhar S, Liu Y. Essential role of integrin-linked kinase in podocyte biology: bridging the integrin and slit diaphragm signaling. J Am Soc Nephrol 2006; 17: 2164–2175
  • Whiteside C I, Cameron R, Munk S, Levy J. Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. Am J Pathol 1993; 142: 1641–1653
  • Bariety J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A. Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 1998; 53: 918–925
  • Vogelmann S U, Nelson W J, Myers B D, Lemley K V. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol 2003; 285: F40–F48
  • Kretzler M. Regulation of adhesive interaction between podocytes and glomerular basement membrane. Microsc Res Tech 2002; 57: 247–253
  • Chen H C, Appeddu P A, Parsons J T, Hildebrand J D, Schaller M D, Guan J L. Interaction of focal adhesion kinase with cytoskeletal protein talin. J Biol Chem 1995; 270: 16995–16999
  • Schrijvers B F, Flyvbjerg A, De Virese A S. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 2004; 65: 2003–2017
  • Datta K, Li J, Karumanchi S A, Wang E, Rondeau E, Mukhopadhyay D. Regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) expression in podocytes. Kidney Int 2004; 66: 1471–1478
  • Freeburg P B, Robert B, St. John P L, Abrahamson D R. Podocyte expression by hypoxia-inducible factor (HIF)-1 and HIF-2 during glomerular development. J Am Soc Nephrol 2003; 14: 927–938
  • Satchell S C, Harper S J, Tooke J E, Kerjaschki D, Saleem M A, Mathieson P W. Human podocytes express angiopoietin 1, a potential regulator of glomerular vascular endothelial growth factor. J Am Soc Nephrol 2002; 13: 544–550
  • Kang D H, Johnson R J. Vascular endothelial growth factor: a new player in the pathogenesis of renal fibrosis. Curr Opin Nephrol Hypertens 2003; 12: 43–49
  • Shulman K, Rosen S, Tognazzi K, Manseau E J, Brown L F. Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol 1996; 7: 661–666
  • Liang X B, Ma L J, Naito T, Wang Y, Madaio M, Zent R, Pozzi A, Fogo A B. Angiotensin type 1 receptor blocker restores podocyte potential to promote glomerular endothelial cell growth. J Am Soc Nephrol 2006; 17: 1886–1895
  • Eremina V, Cui S, Gerber H, Ferrara N, Haigh J, Nagy A, Ema M, Rossant J, Jothy S, Miner J H, Quaggin S E. Vascular endothelial growth factor A signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol 2006; 17: 724–735
  • Noris M, Perico N, Remuzzi G. Mechanisms of disease: preeclampsia. Nat Clin Pract Nephrol 2005; 1: 98–114
  • Maynard S, Min J Y, Merchan J, Lim K H, Li J, Mondal S, Libermann T A, Morgan J P, Sellke F W, Stillman I E, Epstein F H, Sukhatme V P, Karumanchi S A. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003; 111: 649–658
  • Lindheimer M D. Unraveling the mysteries of preeclampsia. Am J Obstet Gynecol 2005; 193: 3–4
  • Bdolah Y, Palomaki G E, Yaron Y, Bdolah-Abram T, Goldman M, Levine R J, Sachs B P, Haddow J E, Karumanchi S A. Circulating angiogenic proteins in trisomy 13. Am J Obstet Gynecol 2006; 194: 239–245
  • Yang J C, Haworth L, Sherry R M, Hwu P, Schwartzentruber D J, Topalian S L, Steinberg S M, Chen H X, Rosenberg S A. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349: 427–434
  • Zhu X, Wu S, Dahut W, Parikh C R. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 2007; 49: 186–193
  • Baelde H J, Eikmans M, Lappin D W, Doran P P, Hohenadel D, Brinkkoetter P T, van der Woude F J, Waldherr R, Rabelink T J, de Heer E. Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss. Kidney Int 2007; 71: 637–645
  • Kobayashi N, Gao S, Chen J, Saito K, Miyawaki K, Li C Y, Pan L, Saito S, Terashita T, Matsuda S. Process formation of the renal glomerular podocyte: is there common molecular machinery for processes of podocytes and neurons. Anat Sci Int 2004; 79: 1–10
  • Rastaldi M P, Armelloni S, Berra S, Calvaresi N, Corbelli A, Giardino L A, Li M, Wang G O, Fornasieri A, Villa A, Heikkila E, Soliymani R, Boucherot A, Cohen C D, Kretzler M, Nitsche A, Ripamonti M, Malgaroli A, Pesaresi M, Forloni G L, Schlondorff D, Holthofer H, D'Amico G. Glomerular podocytes contain neuron-like functional synaptic vesicles. FASEB J 2006; 20: 976–978
  • Beltcheva O, Kontusaari S, Fetissov S, Putaala H, Kilpelainen P, Hokfelt T, Tryggvason K. Alternatively used promoters and distinct elements direct tissue-specific expression of nephrin. J Am Soc Nephrol 2003; 14: 352–358
  • Kobayashi N, Reiser J, Kriz W, Kuriyama R, Mundel P. Non-uniform microtubular polarity, established by CHO1/MKLP1 motor protein, is necessary for process formation of podocytes. J Cell Biol 1998; 143: 1961–1970
  • Simons M, Saffrich R, Reiser J, Mundel P. Directed membrane transport is involved in process formation in cultured podocytes. J Am Soc Nephrol 1999; 10: 1633–1639
  • Rastaldi M P, Armelloni S, Berra S, Li M, Pesaresi M, Poczewski H, Langer B, Kerjaschki D, Henger A, Blattner S M, Kretzler M, Wanke R, D'Amico G. Glomerular podocytes possess the synaptic vesicle molecule Rab3A and its specific effector Rabphilin-3a. Am J Pathol 2003; 163: 889–899
  • Cormont M, Meton I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw T E, Le Marchand-Brustel Y. CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Traffic 2003; 4: 97–112
  • Peitsch W K, Hofmann I, Endlich N, Pratzel S, Kuhn C, Spring H, Grone H J, Kriz W, Franke W W. Cell biological and biochemical characterization of drebrin complexes in mesangial cells and podocytes of renal glomeruli. J Am Soc Nephrol 2003; 14: 1452–1463
  • Gloy J, Reitinger S, Fischer K G, Schreiber R, Boucherot A, Kunzelmann K, Mundel P, Pavenstadt H. Amino acid transporter in podocytes. Am J Physiol Renal Physiol 2000; 278: F999–F1005
  • Thomas P E, Wharram B L, Goyal M, Wiggins J E, Holzman L B, Wiggins R C. GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. J Biol Chem 1994; 269: 19953–19962
  • Yang D H, Goyal M, Sharif K, Kershaw D, Thomas P, Dysko R, Wiggins R. Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man. Lab Invest 1996; 74: 571–584
  • Wharram B L, Goyal M, Gillespie P J, Wiggins J E, Kershaw D G, Holzman L B, Dysko R C, Saunders T L, Samuelson L C, Wiggins R C. Altered podocyte structure in GLEPP1 (Pt-pro)-deficient mice associated with hypertension and low glomerular filtration rate. J Clin Invest 2000; 106: 1281–1290
  • Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, Reiser J, Mundel P. Synaptopodin regulates the actin-bundling activity of α -actinin in an isoform-specific manner. J Clin Invest 2005; 115: 1188–1198
  • Deller T, Korte M, Chabanis S, Drakew A, Schwegler H, Stefani G G, Zuniga A, Schwarz K, Bonhoeffer T, Zeller R, Frotscher M, Mundel P. Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc Natl Acad Sci USA 2003; 100: 10494–10499
  • Kemeny E, Durmuller U, Nickeleit V, Gudat F, Mihatsch M J. Distribution of podocyte protein (44 KD) in different types of glomerular diseases. Virchows Arch 1997; 431: 425–430
  • Paul M D, Fernandez D, Pryse-Phillips W, Gault M H. Charcot-Marie-Tooth disease and nephropathy in a mother and daughter with a review of the literature. Nephron 1990; 54: 80–85
  • Plaisier E, Mougenot B, Verpont M C, Jouanneau C, Archelos J J, Martini R, Kerjaschki D, Ronco P. Glomerular permeability is altered by loss of P0, a myelin protein expressed in glomerular epithelial cells. J Am Soc Nephrol 2005; 16: 3350–3364
  • Gross O, Beirowski B, Harvey S J, McFadden C, Chen D, Tam S, Thorner P S, Smyth N, Addicks K, Bloch W, Ninomiya Y, Sado Y, Weber M, Vogel W F. DDR1-deficient mice show localized subepithelial GBM thickening with focal loss of slit diaphragms and proteinuria. Kidney Int 2004; 66: 102–111
  • Miyauchi N, Saito A, Karasawa T, Harita Y, Suzuki K, Koike H, Han G D, Shimizu F, Kawachi H. Synaptic vesicle protein 2B is expressed in podocyte, and its expression is altered in proteinuric glomeruli. J Am Soc Nephrol 2006; 17: 2748–2759
  • Guan F, Villegas G, Teichman J, Mundel P, Tufro A. Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival. Kidney Int 2006; 69: 1564–1569
  • Tamagnone L, Comoglio P M. To move or not to move? Semaphorin signalling in cell migration. EMBO Rep 2004; 5: 356–361
  • Kriz W. TRPC6—a new podocyte gene involved in focal segmental glomerulosclerosis. Trends Mol Med 2005; 11: 527–530
  • Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional interrelationship in glomerular filtration. Hum Mol Genet 2002; 11: 379–388
  • Caridi G, Bertelli R, Carrea A, Di Duca M, Catarsi P, Artero M, Carraro M, Zennaro C, Candiano G, Musante L, Seri M, Ginevri F, Perfumo F, Ghiggeri G M. Prevalence, genetics, and clinical features of patients carrying podocin mutations in steroid-resistant nonfamilial focal segmental glomerulosclerosis. J Am Soc Nephrol 2001; 12: 2742–2746
  • Karle S M, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A. Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2002; 13: 388–393
  • Tsukaguchi H, Yager H, Dawborn J, Jost L, Cohlmia J, Abreu P F, Pereira A B, Pollak M R. A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25-31. J Am Soc Nephrol 2000; 11: 1674–1680
  • Weber S, Gribouval O, Esquivel E L, Moriniere V, Tete M J, Ledendre C, Niaudet P, Antignac C. NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int 2004; 66: 571–579
  • Caridi G, Perfumo F, Ghiggeri G M. NPHS2 (podocin) mutations in nephrotic syndrome. Clinical spectrum and fine mechanisms. Pediatr Res 2005; 57: 54R–61R
  • He N, Zahirieh A, Mei Y, Lee B, Senthilnathan S, Wong B, Mucha B, Hildebrandt F, Cole D E, Cattran D, Pei Y. Recessive NPHS2 (podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2007; 2: 31–37
  • Ruf R G, Lichtenberger A, Karle S M, Haas J P, Anacleto F E, Schultheiss M, Zalewski I, Imm A, Ruf E M, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004; 15: 722–732
  • Vincenti F, Ghiggeri G M. New insights into the pathogenesis and therapy of recurrent focal glomerulosclerosis. Am J Transplant 2005; 5: 1179–1185
  • Becker-Cohen R, Bruschi M, Rinat C, Feinstein S, Zennaro C, Ghiggeri C M, Frishberg Y. Recurrent nephrotic syndrome in homozygous truncating NPHS2 mutation is not due to anti-podocin antibodies. Am J Transplant 2007; 7: 256–260
  • Frishberg Y, Feinstein S, Rinat C, Becker-Cohen R, Lerer I, Raas-Rothschild A, Ferber B, Nir A. The heart of children with steroid-resistant nephrotic syndrome: is it all podocin?. J Am Soc Nephrol 2006; 17: 227–231
  • Blum S, Nakhoul F, Khankin E, Abassi Z. Renal slit diaphragm—the open zipper and the failing heart. Isr Med Assoc J 2007; 9: 107–111
  • Pereira A C, Pereira A B, Mota G F, Cunha R S, Herkenhoff F L, Pollak M R, Mill J G, Krieger J E. NPHS2 R229Q functional variant is associated with microalbuminuria in the general population. Kidney Int 2004; 65: 1026–1030
  • Franceschini N, North K E, Kopp J B, McKenzie L, Winkler C. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med 2006; 8: 63–75
  • Kaplan J M, Kim S H, North K N, Rennke H, Correia L A, Tong H Q, Mathis B J, Rodriguez-Perez J C, Allen P G, Beggs A H, Pollak M R. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 2000; 24: 251–256
  • Kos C H, Le T C, Sinha S, Henderson J M, Kim S H, Sugimoto H, Kalluri R, Gerszten R E, Pollak M R. Mice deficient in α -actinin-4 have severe glomerular disease. J Clin Invest 2003; 111: 1683–1690
  • Michaud J L, Chaisson K M, Parks R J, Kennedy C R. FSGS-associated α -actinin-4 (K256E) impairs cytoskeletal dynamics in podocytes. Kidney Int 2006; 70: 1054–1061
  • Yao J, Le T C, Kos C H, Henderson J M, Allen P G, Denker B M, Pollak M R. Alpha-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. PloS Biol 2004; 2: e167
  • Winn M, Conlon P, Lynn K, Howell D N, Slotterbeck B D, Smith A H, Graham F L, Bembe M, Quarles L D, Pericak-Vance M A, Vance J M. Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. Genomics 1999; 58: 113–120
  • Möller C C, Wei C, Altintas M M, Li J, Greka A, Ohse T, Pippin J W, Rastaldi M P, Wawersik S, Schiavi S, Henger A, Kretzler M, Shankland S J, Reiser J. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol 2007; 18: 29–36
  • Kim J M, Wu H, Green G, Winkler C A, Kopp J B, Miner J H, Unanue E R, Shaw A S. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science 2003; 300: 1298–1300
  • Huber T B, Kwoh C, Wu H, Asanuma K, Godel M, Hartleben B, Blumer K J, Miner J H, Mundel P, Shaw A S. Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J Clin Invest 2006; 116: 1337–1345
  • Hinkes B, Wiggins R C, Gbadegesin R, Vlangos C N, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins B E, Ashraf S, Becker C, Hennies H C, Goyel M, Wharram B L, Schachter A D, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkalolu A, Cleper R, Base-Vanagaite L, Pohl M, Griebel M, Tsygin A N, Soylu A, Muller D, Sorli C S, Bunney T D, Katan M, Liu J, Attanasio M, O'Toole J F, Hasselbacher K, Mucha B, Otto E A, Airik R, Kispert A, Kelley G G, Smrcka A V, Gudermann T, Holzmann L B, Nurnberg P, Hildebrandt F. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Gen 2006; 38: 1397–1405
  • Bunney T D, Katan M. Phospholipase C epsilon: linking second messengers and small GTPases. Trends Cell Biol 2006; 16: 640–648
  • Wang H, Oestreich E A, Maekawa N, Bullard T A, Vikstrom K L, Dirksen R T, Kelley G G, Blaxall B C, Smrcka A V. Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and inhibits cardiac hypertrophy. Circ Res 2005; 97: 1305–1313
  • Bongers E M, Gubler M C, Knoers N V. Nail-patella syndrome: overview on clinical and molecular findings. Pediatr Nephrol 2002; 17: 703–712
  • Wuhl E, Kogan J, Zurowska A, Matejas V, Vandevoorde R G, Aigner T, Wendler O, Lesniwska I, Bouvier R, Reis A, Weis J, Cochat P, Zenkter M. Neurodevelopmental deficits in Pierson (microcoria-congenital nephrosis) syndrome. Am J Med Genet 2007; 15: 311–319
  • Arfeen S, Rosborough D, Luger A M, Nolph K D. Familial unilateral renal agenesis and focal and segmental glomerulosclerosis. Am J Kidney Dis 1993; 21: 663–668
  • Pelletier J, Bruening W, Kashtan C E, Mauer S M, Manivel J C, Striegel J E, Houghton D C, Junien C, Habib R, Fouser L. Germline mutations in the Wilms tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 1991; 67: 437–447
  • Orloff M S, Iyengar S K, Winkler C A, Dart R A, Ahuja T S, Mokrzycki M, Briggs W A, Korbet S M, Kimmel P L, Simon E E, Trachtman H, Vlahov D, Michel D M, Berns J S, Smith M C, Schelling J R, Sedor J R, Goddard K A, Kopp J B. Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population. Physiol Genomics 2005; 21: 212–221
  • Kambham N, Tanji N, Seigle R L, Markowitz G S, Pulkkinen L, Uitto J, D'Agati V D. Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa. Am J Kidney Dis 2000; 36: 190–196
  • Comper W D, Glasgow E F. Charge selectivity in kidney ultrafiltration. Kidney Int 1995; 47: 1242–1251
  • Goode N P, Shires M, Davison A M. The glomerular basement membrane charge-selectivity barrier: an oversimplified concept?. Nephrol Dial Transplant 1996; 11: 1714–1716
  • Bridges C R, Myers B D, Brenner B M, Deen W M. Glomerular charge alterations in human minimal change nephropathy. Kidney Int 1982; 22: 677–684
  • Shemesh O, Ross J C, Deen W M, Grant G W, Myers B D. Nature of the glomerular capillary injury in human membranous glomerulopathy. J Clin Invest 1986; 77: 868–877
  • Myers B D, Guasch A. Mechanisms of proteinuria in nephrotic humans. Pediatr Nephrol 1994; 8: 107–112
  • Lahdenkari A T, Lounatmaa K, Patrakka J, Holmberg C, Wartiovaara J, Kestila M, Koskimies O, Jalanko H. Podocytes are firmly attached to glomerular basement membrane in kidneys with heavy proteinuria. J Am Soc Nephrol 2004; 15: 2611–2618
  • Shah S, Baliga R, Rajapukar M, Fonseca V A. Oxidants in chronic kidney disease. J Am Soc Nephrol 2007; 18: 16–28
  • Hagiwara M, Yamagata K, Capaldi R A, Koyama A. Mitochondrial dysfunction in focal segmental glomerulosclerosis of puromycin aminonucleoside nephrosis. Kidney Int 2006; 69: 1146–1152
  • Ricardo S D, Bertram J F, Ryan G B. Reactive oxygen species in puromycin aminonucleoside nephrosis: in vitro studies. Kidney Int 1994; 45: 1057–1069
  • Ricardo S D, Bertram J F, Ryan G B. Antioxidants protect podocyte foot processes in puromycin aminonucleoside-treated rats. J Am Soc Nephrol 1994; 4: 1974–1986
  • Zima T, Tesar V, Crkovska J, Stejskalova A, Platenik J, Teminova J, Nemecek K, Janebova M, Stipek S. ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats. Nephrol Dial Transplant 1998; 13: 1975–1979
  • Koshikawa M, Mukoyama M, Mori K, Saganami T, Sawai K, Yoshioka T, Nagae T, Yokoi H, Kawachi H, Shimizu F, Sugiwara A, Nakao K. Role of p38 mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome. J Am Soc Nephrol 2005; 16: 2690–2701
  • Luimula P, Ahola H, Wang S X, Solin M L, Aaltonen P, Tikkanen I, Kerjaschki D, Holthofer H. Nephrin in experimental glomerular disease. Kidney Int 2000; 58: 1461–1468
  • Shaloub R J. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 1974; 2: 556
  • Savin V J, Sharma R, Sharma M, McCarthy E T, Swan S K, Ellis E, Lovell H, Warady B, Gunwar S, Chonko A M, Artero M, Vincenti F. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334: 878–883
  • Garin E H. Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol 2000; 14: 872–878
  • Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y, Hurault de Ligny B, Niaudet P, Charpentier B, Soulillou J P. Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N Engl J Med 1994; 330: 7–14
  • Sharma M, Sharma R, McCarthy E T, Savin V J. “The FSGS factor”: enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol 1999; 10: 552–561
  • Trachtman H, Futterweit S, Singhal P C, Franki N, Sharma M, Sharma R, Savin V. Circulating factor in patients with recurrent focal segmental glomerulosclerosis postrenal transplantation inhibits expression of inducible nitric oxide synthase and nitric oxide production by cultured rat mesangial cells. J Invest Med 1999; 47: 114–120
  • Koyama A, Fukisaki M, Kobayashi M, Igarashi M, Narita M. A glomerular permeability factor produced by human T cell hybridomas. Kidney Int 1991; 40: 453–460
  • Sahali D, Pawlak A, Valanciuté A, Grimbert P, Lang P, Remy P, Bensman A, Guellaen G. A novel approach to investigation of the pathogenesis of active minimal-change nephrotic syndrome using subtracted cDNA library screening. J Am Soc Nephrol 2002; 13: 1238–1247
  • Cunard R, Kelly C J. T cells and minimal change disease. J Am Soc Nephrol 2002; 13: 1409–1411
  • Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R, Zennaro C, Musante L, Candiano G, Perfumo F, Ghiggeri G M. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2002; 13: 1946–1952
  • Cattran D, Neogi T, Sharma R, McCarthy E T, Savin V J. Serial estimates of serum permeability activity and clinical correlates in patients with native kidney focal segmental glomerulosclerosis. J Am Soc Nephrol 2003; 14: 448–453
  • Sharma R, Sharma M, McCarthy E T, Ge X L, Savin V J. Components of normal serum block the focal segmental glomerulosclerosis factor activity in vitro. Kidney Int 2000; 58: 1973–1979
  • Candiano G, Musante L, Carraro M, Faccini L, Campanacci L, Zennaro C, Artero M, Ginevri F, Perfumo F, Gusmano R, Ghiggeri G M. Apolipoproteins prevent glomerular albumin permeability induced in vitro by serum from patients with focal segmental glomerulosclerosis. J Am Soc Nephrol 2001; 12: 143–150
  • Ghiggeri G M, Artero M, Carraro M, Perfumo F. Permeability plasma factors in nephrotic syndrome: more than one factor, more than one inhibitor. Nephrol Dial Transplant 2001; 16: 882–885
  • Musante L, Candiano G, Bruschi M, Zennaro C, Carrato M, Artero M, Giuffrida M G, Conti A, Santucci A, Ghiggeri G M. Characterization of plasma factors that alter the permeability to albumin within isolated glomeruli. Proteomics 2002; 2: 197–205
  • Ghiggeri G M, Bruschi M, Candiano G, Rastaldi M P, Scolari F, Passerini P, Musante L, Pertica N, Caridi G, Ferrario F, Perfumo F, Ponticelli C. Depletion of clusterin in renal diseases causing nephrotic syndrome. Kidney Int 2002; 62: 2184–2194
  • Carraro M, Zennaro C, Candiano G, Musante L, Bruschi M, Ghiggeri G M, Artero M, Faccini L. Nephrotic urine prevents increased rat glomerular albumin permeability induced by serum from the same patient with idiopathic nephrotic syndrome. Nephrol Dial Transplant 2003; 18: 689–693
  • Sharma M, Sharma R, McCarthy E T, Savin V J. The focal segmental glomerulosclerosis permeability factor: biochemical characteristics and biological effects. Exp Biol Med 2004; 229: 85–98
  • Doublier S, Musante L, Lupia E, Candiano G, Spatola T, Caridi G, Zennaro C, Carraro M, Ghiggeri G M, Camussi G. Direct effect of plasma permeability factors from patients with idiopathic FSGS on nephrin and podocin expression in human podocytes. Int J Mol Med 2005; 16: 49–58
  • Marszal J, Saleem M A. The bioactivity of plasma factors in focal segmental glomerulosclerosis. Nephron Exp Nephrol 2006; 104: e1–e5
  • Furness P N, Hall L L, Shaw J A, Pringle J H. Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. Nephrol Dial Transplant 1999; 14: 1234–1237
  • Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H. Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol 2001; 12: 289–296
  • Koop K, Eikmans M, Baelde H J, Kawachi H, de Heer E, Leendert C P, Bruijn J A. Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol 2003; 14: 2063–2071
  • Mao J, Zhang Y, Du L, Dai Y, Yang C, Liang L. Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy. Pediatr Nephrol 2006; 21: 1666–1675
  • Schmid H, Henger A, Cohen C D, Frach K, Grone H J, Schlondorff D, Kretzler M. Gene expression profiles of podocyte-associated molecules as diagnostic markers in acquired proteinuric diseases. J Am Soc Nephrol 2003; 14: 2958–2966
  • Szeto C C, Lai K B, Chow K M, Szeto C Y, Yip T W, Woo K S, Li P K, Lai F M. Messenger RNA expression of glomerular podocyte markers in the urinary sediment of acquired proteinuric diseases. Clin Chim Acta 2005; 361: 182–190
  • Sharif K, Goyal M, Kershaw D, Kunkel R, Wiggins R. Podocyte phenotypes as defined by expression and distribution of GLEPP-1 in the developing glomerulus and in nephrotic glomeruli from MCD, CNF, and FSGS. A dedifferentiation hypothesis for the nephrotic syndrome. Exp Nephrol 1998; 6: 234–244
  • Devarajan P, Spitzer A. Towards biological characterization of focal segmental glomerulosclerosis. Am J Kidney Dis 2002; 39: 625–636
  • Tanawattanacharoen S, Falk R, Jennette C, Kopp J B. Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis. Am J Kidney Dis 2000; 35: 1166–1174
  • Ingulli E, Tejani A. Incidence, treatment and outcome of recurrent focal segmental glomerulosclerosis posttransplantation in 42 allografts in children: a single-center experience. Transplantation 1991; 51: 401–405
  • Artero M L, Sharma R, Savin V J, Vincenti F. Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis. Am J Kidney Dis 1994; 23: 574–581
  • Feld S M, Figueroa P, Savin V, Nast C C, Sharma R, Sharma M, Hirschberg R, Adler S G. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys. Am J Kidney Dis 1998; 32: 230–237
  • Srivastava T, Garola R E, Whiting J M, Alon U S. Synaptopodin expression in idiopathic nephrotic syndrome of childhood. Kidney Int 2001; 59: 118–125
  • Mrowka C, Schedl A. Wilms tumor suppressor gene WT1: from structure to renal pathophysiologic features. J Am Soc Nephrol 2000; 11(Suppl 16)S106–S115
  • Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Apoptosis in glomerular sclerosis. Kidney Int 1996; 49: 103–111
  • Ortiz A. Apoptotic regulatory proteins in renal injury. Kidney Int 2000; 58: 467–485
  • Mayo M W, Wang C Y, Drouin S S, Madrid L V, Marshall A F, Reed J C, Weissman B E, Baldwin A S. WT1 modulates apoptosis by transcriptionally upregulating the bcl-2 proto-oncogene. EMBO J 1999; 18: 3990–4003
  • Schiffer M, Bitzer M, Roberts I S, Kopp J B, ten Dijke P, Mundel P, Bottinger E P. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest 2001; 108: 807–816
  • Wharram B L, Goyal M, Wiggins J E, Sanden S K, Hussain S, Filipiak W E, Saunders T L, Dysko R C, Kohno K, Hozman L B, Wiggins R C. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 2005; 16: 2941–2952
  • Schwab K, Witte D P, Aronow B J, Devarajan P, Potter S C, Patterson L T. Microarray analysis of focal segmental glomerulosclerosis. Am J Nephrol 2004; 24: 438–447
  • Albaqumi M, Soos T J, Barisoni L, Nelson P J. Collapsing glomerulopathy. J Am Soc Nephrol 2006; 17: 2854–2863
  • Barisoni L, Mokrzycki M, Sablay L, Nagata M, Yamase H, Mundel P. Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Kidney Int 2000; 58: 137–143
  • Shah S N, He C J, Klotman P. Update on HIV-associated nephropathy. Curr Opin Nephrol Hypertens 2006; 15: 450–455
  • Husain M, D'Agati V, He J C, Klotman M E, Klotman P E. HIV-1 Nef induces dedifferentiation of podocytes in vivo: a characteristic feature of HIVAN. AIDS 2005; 19: 1975–1980
  • Doublier S, Zennaro C, Spatola T, Lupia E, Bottelli A, Deregibus M C, Carraro M, Conaldi P G, Camussi G. HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy. AIDS 2007; 21: 423–432
  • Nelson P J, Shankland S J. Therapeutics in renal disease: The road ahead for antiproliferative targets. Nephron Exp Nephrol 2006; 103: e6–e15
  • Gherardi D, D'Agati V, Chu T H, Barnett A, Gianella-Borradori A, Gelman I H, Nelson P J. Reversal of collapsing glomerulopathy in mice with the cyclin-dependent kinase inhibitor CYC202. J Am Soc Nephrol 2004; 15: 1212–1222
  • Soos T J, Meijer L, Nelson P J. CDK/GSK-3 inhibitors as a new approach for the treatment of proliferative renal diseases. Drug News Perspect 2006; 19: 314–317
  • Vaughan M R, Pippin J, Griffin S V, Kroft R, Fleet M, Haseley L, Shankland S J. ATRA induces podocyte differentiation and alters nephrin and podocin expression in vitro and in vivo. Kidney Int 2005; 68: 133–144
  • Hermann M, Shaw S, Kiss E, Camici G, Buhler N, Chenevard R, Luscher T F, Grone H J, Ruschitzka F. Selective COX-2 inhibitors and renal injury in salt-sensitive hypertension. Hypertension 2005; 45: 193–197
  • Heckmann A, Waltzinger C, Jolicoeur P, Dreano M, Kosco-Vilbois M H, Sagot Y. IKK2 inhibitor alleviates kidney and wasting diseases in a murine model of human AIDS. Am J Pathol 2004; 164: 1253–1262
  • Chen H M, Liu Z H, Zeng C H, Li S J, Wang Q W, Li L S. Podocyte lesions in patients with obesity-related glomerulopathy. Am J Kidney Dis 2006; 48: 772–779
  • White K E, Bilous R W, Marshall S M, El Nahas M, Remuzzi G, Piras G, De Cosmo S, Viberti G. Podocyte number in normotensive type 1 diabetic patients with albuminuria. Diabetes 2002; 51: 3083–3089
  • Kriz W, Gretz N, Lemley K V. Progression of glomerular diseases: is the podocyte the culprit?. Kidney Int 1998; 54: 687–697
  • Kriz W. Podocyte is the major culprit accounting for the progression of chronic disease. Microvasc Res Tech 2002; 57: 189–195
  • Kambham N, Markowitz G S, Valeri A M, Lin J, D'Agati V D. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 2001; 59: 1498–1509
  • Praga M. Obesity—a neglected culprit in renal disease. Nephrol Dial Transplant 2002; 17: 1157–1159
  • Pagtalunan M E, Miller P L, Jumping-Eagle S, Nelson R G, Myers B D, Rennke H G, Coplon N S, Sun L, Meyer T W. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 1997; 99: 342–348
  • Kerjaschki D, Farquhar M G. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA 1982; 79: 5557–5561
  • Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann J P, Bensman A, Deschenes G, Ronco P M. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med 2002; 346: 2053–2060
  • Ronco P, Debiec H. Molecular dissection of target antigens and nephritogenic antibodies in membranous nephropathy: towards epitope-driven therapies. J Am Soc Nephrol 2006; 17: 1772–1774
  • Nangaku M, Shankland S J, Couser W G. Cellular response to injury in membranous nephropathy. J Am Soc Nephrol 2005; 16: 1195–1204
  • Salant D J, Belok S, Madaio M P, Couser W G. A new role for complement in experimental membranous nephropathy in rats. J Clin Invest 1980; 66: 1339–1350
  • Baker P J, Ochi R F, Schulze M, Johnson R J, Campbell C, Couser W G. Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats. Am J Pathol 1989; 135: 185–194
  • Matsuo S, Morita Y, Yuzawa Y, Maruyama S. Urinary membrane attack complex (MAC) is a potent predictor of poor renal outcome in proteinuric glomerular diseases. J Am Soc Nephrol 2004; 15: 328A, abstract
  • Greiber S, Munzel T, Kastner S, Muller B, Schollmeyer P, Pavenstadt H. NAD(P)H oxidase activity in cultured human podocytes: effects of adenosine triphosphate. Kidney Int 1998; 53: 654–663
  • Takano T, Cybulsky A V, Cupples W A, Ajikobi D O, Papillon J, Aoudjit L. Inhibition of cyclooxygenases reduces complement-induced glomerular epithelial cell injury and proteinuria in passive Heymann nephritis. J Pharmacol Exp Ther 2003; 305: 240–249
  • Minto A W, Kalluri R, Togawa M, Bergijk E C, Killen P D, Salant D J. Augmented expression of glomerular basement membrane specific type IV collagen isoforms (alpha3-alpha5) in experimental membranous nephropathy. Proc Assoc Am Physicians 1998; 110: 207–217
  • Shankland S J, Pippin J, Pichler R H, Gordon K L, Friedman S, Gold L I, Johnson R J, Couser W G. Differential expression of transforming growth factor-beta isoforms and receptors in experimental membranous nephropathy. Kidney Int 1996; 50: 116–124
  • Topham P S, Haydar S A, Kuphal R, Lightfoot J D, Salant D J. Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 1999; 55: 1763–1775
  • Moll S, Lange S, Mihatsch M J, Dragic Z, Schifferli J A, Inal J M. CRIT is expressed on podocytes in normal human kidney and upregulated in membranous nephropathy. Kidney Int 2006; 69: 1961–1968
  • Yuan H, Takeuchi E, Taylor G A, McLaughlin M, Brown D, Salant D J. Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol 2002; 13: 946–956
  • Nakatsue T, Koike H, Han G D, Suzuki K, Miyauchi N, Yuan H, Salant D J, Gejyo F, Shimizu F, Kawachi H. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int 2005; 67: 2239–2353
  • Kim B K, Hong H K, Kim J H, Lee H S. Differential expression of nephrin in acquired human proteinuric diseases. Am J Kidney Dis 2002; 40: 964–973
  • Benigni A, Tomasoni S, Gagliardini E, Zoja C, Grunkemeyer J A, Kalluri R, Remuzzi G. Blocking angiotensin II synthesis/activity preserves glomerular nephrin in rats with severe nephrosis. J Am Soc Nephrol 2001; 12: 941–948
  • Nitschke R, Henger A, Ricken S, Gloy J, Muller V, Greger R, Pavenstadt H. Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus. Kidney Int 2000; 57: 41–49
  • Remuzzi A, Monaci N, Bonassi M E, Corna D, Zoja C, Mohammed E I, Remuzzi G. Angiotensin-converting enzyme inhibition prevents loss of glomerular hydraulic permeability in passive Heymann nephritis. Lab Invest 1999; 79: 1501–1510
  • Ding G, Reddy K, Kapasi A A, Franki N, Gibbons N, Kasinath B S, Singhal P C. Angiotensin II induces apoptosis in rat glomerular epithelial cells. Am J Physiol Renal Physiol 2002; 283: F173–F180
  • Nagata M, Yamaguchi Y, Komatsu Y, Ito K. Mitosis and the presence of binucleate cells among glomerular podocytes in diseased human kidneys. Nephron 1995; 70: 68–71
  • Shankland S J, Pippin J, Couser W G. Complement (C5b-9) induces glomerular epithelial cell DNA synthesis but not proliferation in vitro. Kidney Int 1999; 56: 538–548
  • Hara M, Yanagihara T, Kihara I. Apical cell membranes are shed into urine from injured podocytes in IgA nephropathy: proposal of hypothesis about podocyte injury. Nephrology 2004; 9: A51, abstract
  • Kanno K, Kawachi H, Uchida Y, Hara M, Shimizu F, Uchiyama M. Urinary sediment podocalyxin in children with glomerular diseases. Nephron Clin Pract 2003; 95: c91–c99
  • Saleem M. Urine – a mirror of the (glomerular) soul?. Nephron Clin Pract 2003; 95: c75–c76
  • Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, Ebihara I, Koide H. Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. Am J Nephrol 2000; 20: 373–379
  • Gagliardini E, Benigni A, Tomasoni S, Abbate M, Kalluri R, Remuzzi G. Targeted downregulation of extracellular nephrin in human IgA nephropathy. Am J Nephrol 2003; 23: 277–286
  • Qiu L Q, Sinniah R, Hsu S I. Downregulation of Bcl-2 by podocytes is associated with progressive glomerular injury and clinical indices of poor renal prognosis in human IgA nephropathy. J Am Soc Nephrol 2004; 15: 79–90
  • Lemley K V, Lafayette R A, Safai M, Derby G, Blouch K, Squarer A, Myers B D. Podocytopenia and disease severity in IgA nephropathy. Kidney Int 2002; 61: 1475–1485
  • Han T S, Schwartz M M, Lewis E J. Association of glomerular podocytopathy and nephrotic proteinuria in mesangial lupus nephritis. Lupus 2006; 15: 71–75
  • Zheng L, Sinniah R, Hsu S I. In situ glomerular expression of activated NF-κ B in human lupus nephritis and other non-proliferative proteinuric glomerulopathy. Virchows Arch 2006; 448: 172–183
  • Wolf G, Chen S, Ziyadeh F N. From the periphery of the glomerular capillary wall toward the center of disease. Podocyte injury comes of age in diabetic nephropathy. Diabetes 2006; 54: 1626–1634
  • Coimbra T M, Janssen U, Grone H J, Ostendorf T, Kunter U, Schmidt H, Brabant G, Floege J. Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney Int 2000; 57: 162–182
  • Mifsud S A, Allen T J, Bertram J F, Hulthen U L, Kelly D J, Cooper M E, Wilkinson-Berka J L, Gilbert R E. Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade. Diabetologia 2001; 44: 878–882
  • Han S Y, Kang Y S, Jee Y H, Han K H, Cha D R, Kang S W, Han D S. High glucose and angiotensin II increase beta 1 integrin and integrin-linked kinase synthesis in cultured mouse podocytes. Cell Tissue Res 2006; 323: 321–332
  • Yoo T H, Li J J, Kim J J, Jung D S, Kwak S J, Ryu D R, Choi H Y, Kim J S, Kim H J, Han S H, Lee J E, Han D S, Kang S W. Activation of the renin-angiotensin system within podocytes in diabetics. Kidney Int 2007; 71: 1019–1027
  • Huang X R, Chen W Y, Truong L D, Lan H Y, Wang S X. Chymase is upregulated in diabetic nephropathy: implications of an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol 2003; 14: 1738–1747
  • Ziadeh F N. Mediators of diabetic renal disease: the case for TGF-β as the major mediator. J Am Soc Nephrol 2004; 15(Suppl 1)S55–S57
  • Fujimoto M, Maezawa Y, Yokote K, Joh K, Kobayashi K, Kawamura H, Nishimura M, Roberts A B, Saito Y, Mori S. Mice lacking Smad3 are protected against streptozotocin-induced diabetic glomerulopathy. Biochem Biophys Res Commun 2003; 305: 1002–1007
  • Meyer T W, Bennett P H, Nelson R G. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type II diabetes and microalbuminuria. Diabetologia 1999; 42: 1341–1344
  • Dalla Vestra M, Masiero A, Roiter A M, Saller A, Crepaldi G, Fioretto P. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 2003; 52: 1031–1035
  • Hoffmann S, Podlich D, Hahnel B, Kriz W, Gretz N. Angiotensin II type 1 receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats. J Am Soc Nephrol 2004; 15: 1475–1487
  • Gross M L, El-Shakmak A, Szabo A, Koch A, Kuhlmann A, Munter K, Ritz E, Amann K. ACE-inhibitors, but not endothelin receptor blockers prevent podocyte loss in early diabetic nephropathy. Diabetologia 2003; 46: 856–868
  • Kelly D J, Aaltonen P, Cox A J, Rumble J R, Langham R, Panagiotopoulos S, Jerums G, Holthofer H, Gilbert R E. Expression of the slit-diaphragm protein, nephrin, in experimental diabetic nephropathy: differing effects of anti-proteinuric therapies. Nephrol Dial Transplant 2002; 17: 1327–1332
  • Davis B J, Cao Z, de Gasparo M, Kawachi H, Cooper M E, Allen T J. Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension: potential role of nephrin. J Hypertens 2003; 21: 209–216
  • Petermann A T, Pippin J, Krofft R, Blonski M, Griffin S, Durvasula R, Shankland S J. Viable podocytes detach in experimental diabetic nephropathy: potential mechanism underlying glomerulosclerosis. Nephron Exp Nephrol 2004; 98: e114–e123
  • Chen H C, Chen C A, Guh J Y, Chang J M, Shin S J, Lai Y H. Altering expression of alpha3beta1 integrin on podocytes of human and rats with diabetes. Life Sci 2000; 67: 2345–2353
  • Kitsiou P V, Tzinia A K, Stetler-Stevenson W G, Michael A F, Fan W W, Zhou B, Tsilibary E C. Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells. Am J Physiol Renal Physiol 2003; 284: F671–F679
  • Kagami S, Border W A, Ruoslahti E, Noble N A. Coordinated expression of beta 1 integrins and transforming growth factor-beta-induced matrix proteins in glomerulonephritis. Lab Invest 1993; 69: 68–76
  • Suganami T, Mukoyama M, Mori K, Yokoi H, Koshikawa M, Sawai K, Hidaka S, Ebihara K, Tanaka T, Sugawara A, Kawachi H, Vinson C, Ogawa Y, Nakao K. Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy. FASEB J 2005; 19: 127–129
  • Khoshnoodi J, Sigmundsson K, Ofverstedt L G, Skoglund U, Obrink B, Wartiovaara J, Tryggvason K. Nephrin promotes cell-cell adhesion through homophilic interactions. Am J Pathol 2003; 163: 2337–2346
  • De Vriese A S, Tilton R G, Elger M, Stephan C C, Kriz W, Lameire N H. Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 2001; 12: 993–1000
  • Cooper M E, Vranes D, Youssef S, Stacker S A, Cox A J, Rizkalla B, Casley D J, Bach L A, Kelly D J, Gilbert R E. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes. Diabetes 1999; 48: 2229–2239
  • Chen S, Kasama Y, Lee J S, Jim B, Marin M, Ziyadeh F N. Podocyte-derived vascular endothelial growth factor mediates the stimulation of α 3(IV) collagen production by transforming growth factor-β 1 in mouse podocytes. Diabetes 2004; 53: 2939–2949
  • Aaltonen P, Luimula P, Astrom E, Palmen T, Gronholm T, Palojoki E, Jaakkola I, Ahola H, Tikkanen I, Holthofer H. Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy. Lab Invest 2001; 81: 1185–1190
  • Doublier S, Salvidio G, Lupia E, Ruotsalainen V, Verzola D, Deferrari G, Camussi G. Nephrin expression is reduced in human diabetic nephropathy. Evidence for a distinct role for glycated albumin and angiotensin II. Diabetes 2003; 52: 1023–1030
  • Benigni A, Gagliardini E, Tomasoni S, Abbate M, Ruggenenti P, Kalluri R, Remuzzi G. Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy. Kidney Int 2004; 65: 2193–2200
  • Langham R G, Kelly D J, Cox A J, Gow A J, Holthofer H, Gilbert R E. Angiotensin II-induced proteinuria and expression of the podocyte slit pore membrane protein, nephrin. Nephrol Dial Transplant 2004; 19: 262–263
  • Palmen T, Ahola H, Palgi J, Aaltonen P, Luimula P, Wang S, Jaakkola I, Knip M, Otonkoski T, Holthofer H. Nephrin is expressed in the pancreatic beta cells. Diabetologia 2001; 44: 1274–1280
  • Aaltonen P, Rinta-Valkama J, Patari A, Tossavainen P, Palmen T, Kulmala P, Knip M, Holthofer H. Circulating antibodies to nephrin in patients with type 1 diabetes. Nephrol Dial Transplant 2007; 22: 146–153
  • Jafar T H, Stark P C, Schmid C H, Landa M, Maschio G, Marcantoni C, de Jong P E, de Zeeuw D, Shahinfar S, Ruggenenti P, Remuzzi G, Levey A S, AIPRD Study Group (Angiotensin-Converting Enzyme Inhibition and Progression of Renal Disease). Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int 2001; 60: 1131–1140
  • Gansevoort R T, Sluiter W J, Hemmelder M H, de Zeeuw D, de Jong P E. Antiproteinuric effect of blood-pressure-lowering agents: a metaanalysis of comparative trials. Nephrol Dial Transplant 1995; 10: 1963–1974
  • Don B R, Kaysen G A, Huchison F N, Schambelan M. The effect of angiotensin-converting enzyme inhibition and dietary protein restriction in the treatment of proteinuria. Am J Kidney Dis 1991; 17: 10–17
  • Liebau M C, Lang D, Bohm J, Endlich N, Bek M J, Witherden I, Mathieson P W, Saleem M A, Pavenstadt H, Fischer K G. Functional expression of the renin angiotensin system in human podocytes. Am J Physiol Renal Physiol 2006; 27: F710–F719
  • Adamczak M, Gross M L, Krtil J, Koch A, Tyralla K, Amann K, Ritz E. Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally nephrectomized rats. J Am Soc Nephrol 2003; 14: 2833–2842
  • Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension 2007; 49: 355–364
  • Amann K, Nichols C, Tornig J, Schwarz U, Zeier M, Mall G, Ritz E. Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental chronic renal failure. Nephrol Dial Transplant 1996; 11: 1003–1011
  • Yamauchi K, Takano Y, Kasai A, Hayakawa K, Hiramatsu N, Enomoto N, Yao J, Kitamura M. Screening and identification of substances that regulate nephrin gene expression using engineered reporter podocytes. Kidney Int 2006; 70: 892–900
  • Moreno-Manzano V, Mampaso F, Sepulveda-Munoz J C, Alique M, Chen S, Ziyadeh F N, Iglesias-de la Cruz M C, Rodriguez J, Nieto E, Orellana J M, Reyes P, Ambas I, Xu Q, Kitamura M, Lucio Cazana F J. Retinoids as a potential treatment for experimental puromycin-induced nephrosis. Br J Pharmacol 2003; 139: 823–831
  • He J C, Lu T C, Fleet M, Sunamoto M, Husain M, Fang W, Neves S, Chen Y, Shankland S, Iyengar R, Klotman P E. Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway. J Am Soc Nephrol 2007; 18: 93–102
  • Kuhlmann A, Haas C S, Gross M L, Reulbach U, Holzinger M, Schwarz U, Ritz E, Amann K. 1,25-dihydroxyvitamin D3 decreases podocyte loss and podocyte hypertrophy in the subtotally nephrectomized rat. Am J Physiol Renal Physiol 2004; 286: F526–F533
  • Ransom R F, Lam N G, Hallett M A, Atkinson S J, Smoyer W E. Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int 2005; 68: 2473–2483
  • Ransom R F, Vega-Warner V, Smoyer W E, Klein J. Differential proteomic analysis of proteins induced by glucocorticoids in cultured murine podocytes. Kidney Int 2005; 67: 1275–1285
  • Miyata T, Inagi R, Sugiyama S, Usuda N. Serpinopathy and endoplasmic reticulum stress. Med Mol Morphol 2005; 38: 73–78
  • Inagi R, Nangaku M, Onogi H, Ueyama H, Kitao Y, Nakazato K, Ogawa S, Kurokawa K, Couser W G, Miyata T. Involvement of endoplasmic reticulum (ER) stress in podocyte injury by excessive protein accumulation. Kidney Int 2005; 68: 2639–2650
  • Fujii Y, Khoshnoodi J, Takenaka H, Hosoyamada M, Nakajo A, Bessho F, Kudo A, Takahashi S, Arimura Y, Yamada A, Nagasawa T, Ruotsalainen V, Tryggvason K, Lee A S, Yan K. The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases. Kidney Int 2006; 69: 1350–1359
  • Kim B S, Park H C, Kang S W, Choi K H, Ha S K, Han D S, Lee H Y. Impact of cyclosporin on podocyte ZO-1 expression in puromycin aminonucleoside nephrosis in rats. Yonsei Med J 2005; 46: 141–148
  • Zima T, Tesar V, Stipek S, Crkovska J, Poledne R, Teminova J, Platenik J, Rychlik I, Merta M, Nemecek K. The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats. Nephron 1997; 75: 464–468
  • Hocker B, Knuppel T, Waldherr R, Schaefer F, Weber S, Tonshoff B. Recurrence of proteinuria 10 years post-transplant in NPHS2-associated focal segmental glomerulosclerosis after conversion from cyclosporin A to sirolimus. Pediatr Nephrol 2006; 21: 1476–1479
  • Daniel C, Renders L, Amann K, Schulze-Lohoff E, Hauser I A, Hugo C. Mechanisms of everolimus-induced glomerulosclerosis after glomerular injury in the rat. Am J Transplant 2005; 5: 2849–2861
  • Cho M E, Hurley J K, Kopp J B. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis 2007; 49: 310–317
  • Tonolo G, Velussi M, Brocco E, Abaterusso C, Carraro A, Morgia G, Satta A, Faedda R, Abhyankar A, Luthman H, Nosadini R. Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes. Kidney Int 2006; 70: 177–186
  • Bussolati B, Deregibus M C, Fonsato V, Doublier S, Spatola T, Procida S, Di Carlo F, Camussi G. Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidylinositol 3-kinase/AKT-signaling pathway. J Am Soc Nephrol 2005; 16: 1936–1947
  • Zoja C, Corna D, Rottoli D, Cattaneo D, Zanchi C, Tomasoni S, Abbate M, Remuzzi G. Effect of combining ACE inhibitor and statin in severe experimental nephropathy. Kidney Int 2002; 61: 1635–1645
  • Buemi M, Allegra A, Corica F, Aloisi C, Giacobbe M, Pettinato G, Corsonello A, Senatore M, Frisina H. Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy. Clin Pharmacol Ther 2000; 67: 427–431
  • Nakamura T, Ushiyama C, Suzuki S, Shimada N, Sekizuka K, Ebihara L, Koide H. Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentration in type 2 diabetic patients with microalbuminuria or macroalbuminuria. Diabet Med 2001; 18: 308–313
  • Agarwal R, Saha C, Battiwal M, Vasavad N, Curley T, Chase S D, Sachs N, Semret M H. A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy. Kidney Int 2005; 68: 285–292
  • Benigni A, Zoja C, Tomasoni S, Campana M, Corna D, Zanchi C, Gagliardini E, Garofano E, Rottoli D, Ito T, Remuzzi G. Transcriptional regulation of nephrin gene by peroxisome proliferator-activated receptor-γ agonist: molecular mechanism of the antiproteinuric effect of pioglitazone. J Am Soc Nephrol 2006; 17: 1624–1632
  • Suzuki A, Ito T, Imai E, Yamato M, Iwatani H, Kawachi H, Hori M. Retinoids regulate the repairing process of the podocytes in puromycin aminonucleoside-induced nephrotic rats. J Am Soc Nephrol 2003; 14: 981–991
  • Chawla A, Repa J J, Evans R M, Mangelsdorf D J. Nuclear receptors and lipid physiology: opening the X-files. Science 2001; 294: 1866–1870
  • Milovanceva-Popovska M, Kunter U, Ostendorf T, Petermann A, Rong S, Eitner F, Kerjaschki D, Barnett A, Floege J. R-roscovitine (CYC202) alleviates renal cell proliferation in nephritis without aggravating podocyte injury. Kidney Int 2005; 67: 1362–1370
  • Durvasula R B, Shankland S J. Podocyte injury and targeting therapy: an update. Curr Opin Nephrol Hypertens 2006; 15: 1–7

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