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Review Article

Signaling pathways of PAX2 and its role in renal interstitial fibrosis and glomerulosclerosis

Pages 298-303 | Received 16 Sep 2012, Accepted 05 Oct 2012, Published online: 09 Nov 2012

References

  • Luu VD, Boysen G, Struckmann K, Casagrande S, von Teichman A, Wild PJ, Sulser T, Schraml P, Moch H. Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma. Clin Cancer Res 2009, 15, 3297–3304.
  • Kahraman K, Kiremitci S, Taskin S, Kankaya D, Sertcelik A, Ortac F. Expression pattern of PAX2 in hyperplastic and malignant endometrium. Arch Gynecol Obstet 2012, 286, 173–178.
  • Torban E, Goodyer P. What PAX genes do in the kidney. Exp Nephrol 1998, 6, 7–11.
  • Soofi A, Levitan I, Dressler GR. Two novel EGFP insertion alleles reveal unique aspects of Pax2 function in embryonic and adult kidneys. Dev Biol 2012, 365, 241–250.
  • Mazal PR, Stichenwirth M, Koller A, Blach S, Haitel A, Susani M. Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol 2005, 18, 535–540.
  • Hueber PA, Waters P, Clark P, Clarke P, Eccles M, Goodyer P. PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells. Kidney Int 2006, 69, 1139–1145.
  • Tagge EP, Hanson P, Re GG, Othersen HB, Smith CD, Garvin AJ. Paired box gene expression in Wilms’ tumor. J Pediatr Surg 1994, 29, 134–141.
  • Tamimi Y, Dietrich K, Stone K, Grundy P. Paired box genes, PAX-2 and PAX-8, are not frequently mutated in Wilms tumor. Mutat Res 2006, 601, 46–50.
  • Davis JL, Matsumura L, Weeks DA, Troxell ML. PAX2 expression in Wilms tumors and other childhood neoplasms. Am J Surg Pathol 2011, 35, 1186–1194.
  • Khoubehi B, Kessling AM, Adshead JM, Smith GL, Smith RD, Ogden CW. Expression of the developmental and oncogenic PAX2 gene in human prostate cancer. J Urol 2001, 165, 2115–2120.
  • Bose SK, Gibson W, Bullard RS, Donald CD. PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer. Mol Immunol 2009, 46, 1140–1148.
  • Eccles MR, Schimmenti LA. Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. Clin Genet 1999, 56, 1–9.
  • Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R 3rd. Renal-coloboma syndrome: report of a novel PAX2 gene mutation. Am J Ophthalmol 2001, 132, 910–914.
  • Choi KL, McNoe LA, French MC, Guilford PJ, Eccles MR. Absence of PAX2 gene mutations in patients with primary familial vesicoureteric reflux. J Med Genet 1998, 35, 338–339.
  • Murawski IJ, Myburgh DB, Favor J, Gupta IR. Vesico-ureteric reflux and urinary tract development in the Pax2 1Neu+/- mouse. Am J Physiol Renal Physiol 2007, 293, 1736–1745.
  • Cohen T, Loutochin O, Amin M, Capolicchio JP, Goodyer P, Jednak R. PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death. Am J Physiol Renal Physiol 2007, 292, 1267–1273.
  • Huang B, Pi L, Chen C, Yuan F, Zhou Q, Teng J, Jiang T. WT1 and Pax2 re-expression is required for epithelial-mesenchymal transition in 5/6 nephrectomized rats and cultured kidney tubular epithelial cells. Cells Tissues Organs (Print) 2012, 195, 296–312.
  • Li L, Wu Y, Zhang W. PAX2 re-expression in renal tubular epithelial cells and correlation with renal interstitial fibrosis of rats with obstructive nephropathy. Ren Fail 2010, 32, 603–611.
  • Mure PY, Gelas T, Dijoud F, Guerret S, Benchaib M, Hartmann DJ, Mouriquand P. Complete unilateral ureteral obstruction in the fetal lamb. Part II: Long-term outcomes of renal tissue development. J Urol 2006, 175, 1548–1558.
  • Hill GS, Karoui KE, Karras A, Mandet C, Duong Van Huyen JP, Nochy D, Bruneval P. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies. Kidney Int 2011, 79, 635–642.
  • Ohtaka A, Ootaka T, Sato H, Ito S. Phenotypic change of glomerular podocytes in primary focal segmental glomerulosclerosis: developmental paradigm? Nephrol Dial Transplant 2002, 17 Suppl 9, 11–15.
  • Yang Y, Gubler MC, Beaufils H. Dysregulation of podocyte phenotype in idiopathic collapsing glomerulopathy and HIV-associated nephropathy. Nephron 2002, 91, 416–423.
  • Maeshima A, Maeshima K, Nojima Y, Kojima I. Involvement of Pax-2 in the action of activin A on tubular cell regeneration. J Am Soc Nephrol 2002, 13, 2850–2859.
  • Kim D, Wang M, Cai Q, Brooks H, Dressler GR. Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia. J Am Soc Nephrol 2007, 18, 1458–1465.
  • Discenza MT, He S, Lee TH, Chu LL, Bolon B, Goodyer P, Eccles M, Pelletier J. WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2. Oncogene 2003, 22, 8145–8155.
  • Murer L, Caridi G, Della Vella M, Montini G, Carasi C, Ghiggeri G, Zacchello G. Expression of nuclear transcription factor PAX2 in renal biopsies of juvenile nephronophthisis. Nephron 2002, 91, 588–593.
  • Bedell VM, Person AD, Larson JD, McLoon A, Balciunas D, Clark KJ, Neff KI, Nelson KE, Bill BR, Schimmenti LA, Beiraghi S, Ekker SC. The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development. Development 2012, 139, 793–804.
  • Cai Y, Lechner MS, Nihalani D, Prindle MJ, Holzman LB, Dressler GR. Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation. J Biol Chem 2002, 277, 1217–1222.
  • Zhang SL, Moini B, Ingelfinger JR. Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor. J Am Soc Nephrol 2004, 15, 1452–1465.
  • James RG, Kamei CN, Wang Q, Jiang R, Schultheiss TM. Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development 2006, 133, 2995–3004.
  • Shen W, Brown NS, Finn PF, Dice JF, Franch HA. Akt and Mammalian target of rapamycin regulate separate systems of proteolysis in renal tubular cells. J Am Soc Nephrol 2006, 17, 2414–2423.
  • Kobayashi H, Kawakami K, Asashima M, Nishinakamura R. Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric-tubule defects. Mech Dev 2007, 124, 290–303.
  • Chen YW, Liu F, Tran S, Zhu Y, Hébert MJ, Ingelfinger JR, Zhang SL. Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose-induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and kidney explants. Kidney Int 2006, 70, 1607–1615.
  • Zhang SL, Chen YW, Tran S, Chenier I, Hébert MJ, Ingelfinger JR. Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis. J Am Soc Nephrol 2007, 18, 2105–2115.
  • Yang SP, Woolf AS, Yuan HT, Scott RJ, Risdon RA, O’Hare MJ, Winyard PJ. Potential biological role of transforming growth factor-beta1 in human congenital kidney malformations. Am J Pathol 2000, 157, 1633–1647.
  • Gai Z, Zhou G, Itoh S, Morimoto Y, Tanishima H, Hatamura I, Uetani K, Ito M, Muragaki Y. Trps1 functions downstream of Bmp7 in kidney development. J Am Soc Nephrol 2009, 20, 2403–2411.
  • Fujimura S, Jiang Q, Kobayashi C, Nishinakamura R. Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol 2010, 21, 803–810.
  • Fujita H, Hida M, Kanemoto K, Fukuda K, Nagata M, Awazu M. Cyclic stretch induces proliferation and TGF-beta1-mediated apoptosis via p38 and ERK in ureteric bud cells. Am J Physiol Renal Physiol 2010, 299, 648–655.
  • Ryan G, Steele-Perkins V, Morris JF, Rauscher FJ, Dressler GR. Repression of Pax-2 by WT1 during normal kidney development. Development 1995, 121, 867–875.
  • Stayner CK, Cunliffe HE, Ward TA, Eccles MR. Cloning and characterization of the human PAX2 promoter. J Biol Chem 1998, 273, 25472–25479.
  • Dormoy V, Danilin S, Lindner V, Thomas L, Rothhut S, Coquard C, Helwig JJ, Jacqmin D, Lang H, Massfelder T. The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth. Mol Cancer 2009, 8, 123.
  • Xu PX, Zheng W, Huang L, Maire P, Laclef C, Silvius D. Six1 is required for the early organogenesis of mammalian kidney. Development 2003, 130, 3085–3094.
  • Zou D, Silvius D, Rodrigo-Blomqvist S, Enerbäck S, Xu PX. Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear. Dev Biol 2006, 298, 430–441.
  • Cai Y, Brophy PD, Levitan I, Stifani S, Dressler GR. Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation. EMBO J 2003, 22, 5522–5529.
  • Patel SR, Dressler GR. Expression of Pax2 in the intermediate mesoderm is regulated by YY1. Dev Biol 2004, 267, 505–516.
  • Poladia DP, Kish K, Kutay B, Hains D, Kegg H, Zhao H, Bates CM. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol 2006, 291, 325–339.
  • Gao X, Chen X, Taglienti M, Rumballe B, Little MH, Kreidberg JA. Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa. Development 2005, 132, 5437–5449.
  • Torban E, Dziarmaga A, Iglesias D, Chu LL, Vassilieva T, Little M, Eccles M, Discenza M, Pelletier J, Goodyer P. PAX2 activates WNT4 expression during mammalian kidney development. J Biol Chem 2006, 281, 12705–12712.
  • Dziarmaga A, Hueber PA, Iglesias D, Hache N, Jeffs A, Gendron N, Mackenzie A, Eccles M, Goodyer P. Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2. Am J Physiol Renal Physiol 2006, 291, 913–920.
  • Brophy PD, Ostrom L, Lang KM, Dressler GR. Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene. Development 2001, 128, 4747–4756.
  • Sajithlal G, Zou D, Silvius D, Xu PX. Eya 1 acts as a critical regulator for specifying the metanephric mesenchyme. Dev Biol 2005, 284, 323–336.
  • Zhang Z, Quinlan J, Grote D, Lemire M, Hudson T, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Houghton F, Bouchard M, Goodyer P. Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn. Pediatr Nephrol 2009, 24, 1151–1157.
  • Clarke JC, Patel SR, Raymond RM, Andrew S, Robinson BG, Dressler GR, Brophy PD. Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage. Hum Mol Genet 2006, 15, 3420–3428.
  • Tamimi Y, Ekuere U, Laughton N, Grundy P. WNT5A is regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis. Neoplasia 2008, 10, 1470–1480.
  • Xu B, Hariharan A, Rakshit S, Dressler GR, Wellik DM. The role of Pax2 in mouse prostate development. Prostate 2012, 72, 217–224.
  • McConnell MJ, Cunliffe HE, Chua LJ, Ward TA, Eccles MR. Differential regulation of the human Wilms tumour suppressor gene (WT1) promoter by two isoforms of PAX2. Oncogene 1997, 14, 2689–2700.
  • Davies JA, Ladomery M, Hohenstein P, Michael L, Shafe A, Spraggon L, Hastie N. Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. Hum Mol Genet 2004, 13, 235–246.
  • Boualia SK, Gaitan Y, Murawski I, Nadon R, Gupta IR, Bouchard M. Vesicoureteral reflux and other urinary tract malformations in mice compound heterozygous for Pax2 and Emx2. PLoS One 2011, 6, 21529.
  • Brophy PD, Lang KM, Dressler GR. The secreted frizzled related protein 2 (SFRP2) gene is a target of the Pax2 transcription factor. J Biol Chem 2003, 278, 52401–52405.
  • Grote D, Souabni A, Busslinger M, Bouchard M. Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development 2006, 133, 53–61.
  • Doberstein K, Pfeilschifter J, Gutwein P. The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis 2011, 32, 1713–1723.
  • Nakane A, Kojima Y, Hayashi Y, Kohri K, Masui S, Nishinakamura R. Pax2 overexpression in embryoid bodies induces upregulation of integrin alpha8 and aquaporin-1. In Vitro Cell Dev Biol Anim 2009, 45, 62–68.
  • Schedl A, Hastie ND. Cross-talk in kidney development. Curr Opin Genet Dev 2000, 10, 543–549.
  • Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol 2007, 27, 7661–7668.
  • Eccles MR. The role of PAX2 in normal and abnormal development of the urinary tract. Pediatr Nephrol 1998, 12, 712–720.
  • Imgrund M, Gröne E, Gröne HJ, Kretzler M, Holzman L, Schlöndorff D, Rothenpieler UW. Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice 1. Kidney Int 1999, 56, 1423–1431.
  • Rothenpieler UW, Dressler GR. Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development. Development 1993, 119, 711–720.
  • Zhang HQ, Yi ZW, He XJ, Dang XQ, He QN, Mo SH. Pax2 expression in children with steroid-resistant primary nephrotic syndrome. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2005, 30, 597–600.
  • Zhou TB, Qin YH, Lei FY, Zhao YJ, Huang WF. Association of PAX2 with cell apoptosis in unilateral ureteral obstruction rats. Ren Fail 2012, 34, 194–202.
  • Torban E, Eccles MR, Favor J, Goodyer PR. PAX2 suppresses apoptosis in renal collecting duct cells. Am J Pathol 2000, 157, 833–842.
  • Zhang SL, Guo J, Moini B, Ingelfinger JR. Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: impact on proliferation and apoptosis. Kidney Int 2004, 66, 2181–2192.
  • Cai Q, Dmitrieva NI, Ferraris JD, Brooks HL, van Balkom BW, Burg M. Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance. Proc Natl Acad Sci USA 2005, 102, 503–508.
  • Yang Y, Jeanpierre C, Dressler GR, Lacoste M, Niaudet P, Gubler MC. 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.
  • Yi ZW, Fang XL, Wu XC, He XJ, He QN, Dang XQ, Zhu CP, Mo SH. Role of PAX2 gene polymorphisms in Henoch-Schonlein purpura nephritis. Nephrology (Carlton) 2006, 11, 42–48.
  • Wagner KD, Wagner N, Guo JK, Elger M, Dallman MJ, Bugeon L, Schedl A. An inducible mouse model for PAX2-dependent glomerular disease: insights into a complex pathogenesis. Curr Biol 2006, 16, 793–800.
  • Waters AM, Wu MY, Onay T, Scutaru J, Liu J, Lobe CG, Quaggin SE, Piscione TD. Ectopic notch activation in developing podocytes causes glomerulosclerosis. J Am Soc Nephrol 2008, 19, 1139–1157.
  • Ohtsubo H, Morisada N, Kaito H, Nagatani K, Nakanishi K, Iijima K. Alport-like glomerular basement membrane changes with renal-coloboma syndrome. Pediatr Nephrol 2012, 27, 1189–1192.
  • Rui HL, Wang YY, Cheng H, Chen YP. JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-beta1 synthesis in human renal proximal epithelial cells. Am J Physiol Renal Physiol 2012, 302, 1569–1575.
  • de Borst MH, Prakash J, Sandovici M, Klok PA, Hamming I, Kok RJ, Navis G, van Goor H. c-Jun NH2-terminal kinase is crucially involved in renal tubulo-interstitial inflammation. J Pharmacol Exp Ther 2009, 331, 896–905.
  • Surendran K, Simon TC. CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury. Am J Physiol Renal Physiol 2003, 284, 653–662.
  • Surendran K, McCaul SP, Simon TC. A role for Wnt-4 in renal fibrosis. Am J Physiol Renal Physiol 2002, 282, 431–441.
  • Tsui CC, Shankland SJ, Pierchala BA. Glial cell line-derived neurotrophic factor and its receptor ret is a novel ligand-receptor complex critical for survival response during podocyte injury. J Am Soc Nephrol 2006, 17, 1543–1552.
  • Orth SR, Ritz E, Suter-Crazzolara C. Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells. Nephrol Dial Transplant 2000, 15, 589–595.

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