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State-of-the-Art Review

Iron metabolism and chronic inflammation in IgA nephropathy

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Article: 2195012 | Received 09 Nov 2022, Accepted 20 Mar 2023, Published online: 04 Apr 2023

References

  • Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr. 2017;106(Suppl 6):1559S–1566S.
  • Hu Y, Guo N, Yang T, et al. The potential mechanisms by which artemisinin and its derivatives induce ferroptosis in the treatment of cancer. Oxid Med Cell Longev. 2022;2022:1458143.
  • Qu X-X, He J-H, Cui Z-Q, et al. PPAR-α agonist GW7647 protects against oxidative stress and iron deposit via GPx4 in a transgenic mouse model of alzheimer’s diseases. ACS Chem Neurosci. 2022;13(2):207–216.
  • Li J-y, Liu S-Q, Yao R-Q, et al. A novel insight into the fate of cardiomyocytes in Ischemia-Reperfusion injury: from iron metabolism to ferroptosis. Front Cell Dev Biol. 2021;9:799499.
  • Lanser L, Fuchs D, Kurz K, et al. Physiology and inflammation driven pathophysiology of iron Homeostasis-Mechanistic insights into anemia of inflammation and its treatment. Nutrients. 2021;13(11):3732.
  • Mahadea D, Adamczewska E, Ratajczak AE, et al. Iron deficiency anemia in inflammatory bowel Diseases-A narrative review. Nutrients. 2021;13(11):4008.
  • Chen S, Zhu J-y, Zang X, et al. The emerging role of ferroptosis in liver diseases. Front Cell Dev Biol. 2021;9:801365.
  • Takahashi M, Mizumura K, Gon Y, et al. Iron-Dependent mitochondrial dysfunction contributes to the pathogenesis of pulmonary fibrosis. Front Pharmacol. 2022;12:643980.
  • Zhang X, Li X. Abnormal iron and lipid metabolism mediated ferroptosis in kidney diseases and its therapeutic potential. Metabolites. 2022;12(1):58.
  • Martines AMF, Masereeuw R, Tjalsma H, et al. Iron metabolism in the pathogenesis of iron-induced kidney injury. Nat Rev Nephrol. 2013;9(7):385–398.
  • van Swelm RPL, Wetzels JFM, Swinkels DW. The multifaceted role of iron in renal health and disease. Nat Rev Nephrol. 2020;16(2):77–98.
  • van Raaij SEG, Rennings AJ, Biemond BJ, et al. Iron handling by the human kidney: glomerular filtration and tubular reabsorption both contribute to urinary iron excretion. American J Physiol Renal Physiol. 2019;316(3):F606–F614.
  • Scindia Y, Dey P, Thirunagari A, et al. Hepcidin mitigates renal Ischemia-Reperfusion injury by modulating systemic iron homeostasis. J Am Soc Nephrol JASN. 2015;26(11):2800–2814.
  • Scindia Y, Leeds J, Swaminathan S. Iron homeostasis in healthy kidney and its role in acute kidney injury. Semin Nephrol. 2019;39(1):76–84.
  • Gao W, Li X, Gao Z, et al. Iron increases diabetes-induced kidney injury and oxidative stress in rats. Biol Trace Elem Res. 2014;160(3):368–375.
  • Hassler JR. IgA nephropathy: a brief review. Semin Diagnostic Pathol. 2020;37(3):143–147.
  • Schena FP. A retrospective analysis of the natural history of primary IgA nephropathy worldwide. Am J Med. 1990;89(2):209–215.
  • Schena FP, Nistor I. Epidemiology of IgA nephropathy: a global perspective. Sem Nephrol. 2018;38(5):435–442.
  • Moura IC, Arcos-Fajardo M, Sadaka C, et al. Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. J Am Soc Nephrol JASN. 2004;15(3):622–634.
  • Moura IC, Arcos-Fajardo M, Gdoura A, et al. Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy. JASN. 2005;16(9):2667–2676.
  • Delanghe SE, Speeckaert MM, Segers H, et al. Soluble transferrin receptor in urine, a new biomarker for IgA nephropathy and Henoch-Schönlein purpura nephritis. Clin Biochem. 2013;46(7-8):591–597.
  • Han X, Xiao Y, Tang Y, et al. Clinical and pathological features of immunoglobulin a nephropathy patients with nephrotic syndrome. Clin Exp Med. 2019;19(4):479–486.
  • Fan X, Zhang X, Liu LC, et al. Hemopexin accumulates in kidneys and worsens acute kidney injury by causing hemoglobin deposition and exacerbation of iron toxicity in proximal tubules. Kid Inter. 2022;102(6):1320–1330.
  • Sheerin NS, Sacks SH, Fogazzi GB. In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron. Nephrol Dial Transplant. 1999;14(6):1391–1397.
  • Gutiérrez E, Egido J, Rubio-Navarro A, et al. Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy. Nephron Clin Pract. 2012;121(1-2):c42–c53.
  • Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis. 1992;20(1):1–17.
  • Zager RA, Burkhart KM. Differential effects of glutathione and cysteine on Fe2+, Fe3+, H2O2 and myoglobin-induced proximal tubular cell attack. Kidney Int. 1998;53(6):1661–1672.
  • Doguer C, Ha J-H, Collins JF. Intersection of iron and copper metabolism in the mammalian intestine and liver. Comprehen Physiol. 2018;8(4):1433–1461.
  • Nemeth E, Ganz T. Hepcidin-Ferroportin interaction controls systemic iron homeostasis. IJMS. 2021;22(12):6493.
  • Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93(4):1721–1741.
  • Thomas C, Oates PS. Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut. 2004;53(1):44–49.
  • Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341(26):1986–1995.
  • Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A. 1968;61(2):748–755.
  • Soares MP, Hamza I. Macrophages and iron metabolism. Immunity. 2016;44(3):492–504.
  • Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol. 2006;2(8):406–414.
  • Leipuviene R, Theil EC. The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen. Cell Mol Life Sci. 2007;64(22):2945–2955.
  • Brissot P, Ropert M, Le Lan C, et al. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012;1820(3):403–410.
  • Knutson MD. Non-transferrin-bound iron transporters. Free Radical Biol Med. 2019;133:101–111.
  • Liuzzi JP, Aydemir F, Nam H, et al. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA. 2006;103(37):13612–13617.
  • Trinder D. Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload. Gut. 2000;46(2):270–276.
  • Ji C, Kosman DJ. Molecular mechanisms of non-transferrin-bound and transferring-bound iron uptake in primary hippocampal neurons. J Neurochem. 2015;133(5):668–683.
  • Mwanjewe J, Grover AK. Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound iron uptake in neuronal phenotype PC12 cells. Biochem J. 2004;378(Pt 3):975–982.
  • Weiss A, Spektor L, A. Cohen L, et al. Orchestrated regulation of iron trafficking proteins in the kidney during iron overload facilitates systemic iron retention. PLoS ONE. 2018;13(10):e0204471.
  • Smith CP, Lee W-K, Haley M, et al. Proximal tubule transferrin uptake is modulated by cellular iron and mediated by apical membrane megalin-cubilin complex and transferrin receptor 1. J Biol Chem. 2019;294(17):7025–7036.
  • Meyron-Holtz EG, Ghosh MC, Iwai K, et al. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. Embo J. 2004;23(2):386–395.
  • Schödel J, Klanke B, Weidemann A, et al. HIF-prolyl hydroxylases in the rat kidney: physiologic expression patterns and regulation in acute kidney injury. Am J Pathol. 2009;174(5):1663–1674.
  • Shu S, Wang Y, Zheng M, et al. Hypoxia and Hypoxia-Inducible factors in kidney injury and repair. Cells. 2019;8(3):207.
  • Koury MJ, Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol. 2015;11(7):394–410.
  • Tajima S, Tsuchiya K, Horinouchi Y, et al. Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells. Hypertens Res. 2010;33(7):713–721.
  • van Raaij S, van Swelm R, Bouman K, et al. Publisher correction: tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease. Sci Rep. 2018;8(1):13390.
  • Thévenod F, Wolff NA. Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity. Metallomics Integrated Biometal Sci. 2016;8(1):17–42.
  • Norden AG, Lapsley M, Lee PJ, et al. Glomerular protein sieving and implications for renal failure in fanconi syndrome. Kidney Int. 2001;60(5):1885–1892.
  • Vilasi A, Cutillas PR, Maher AD, et al. Combined proteomic and metabonomic studies in three genetic forms of the renal fanconi syndrome. Am J Physiol Renal Physiol. 2007;293(2):F456–F467.
  • Kozyraki R, Fyfe J, Verroust PJ, et al. Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci USA. 2001;98(22):12491–12496.
  • Langelueddecke C, Roussa E, Fenton RA, et al. Lipocalin-2 (24p3/neutrophil gelatinase-associated lipocalin (NGAL)) receptor is expressed in distal nephron and mediates protein endocytosis. J Biol Chem. 2012;287(1):159–169.
  • Haldar S, Tripathi A, Qian J, et al. Prion protein promotes kidney iron uptake via its ferrireductase activity. J Biol Chem. 2015;290(9):5512–5522.
  • van Raaij SEG, Masereeuw R, Swinkels DW, et al. Inhibition of Nrf2 alters cell stress induced by chronic iron exposure in human proximal tubular epithelial cells. Toxicol Lett. 2018;295:179–186.
  • McGonigle RJ, Wallin JD, Shadduck RK, et al. Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int. 1984;25(2):437–444.
  • Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–1023.
  • Inoue A, et al. Albuminuria is an independent predictor of decreased serum erythropoietin levels in type 2 diabetic patients. Nephrol Dial Transplant. 2007;22(1):287–288.
  • Yamaguchi-Yamada M, Manabe N, Uchio-Yamada K, et al. Anemia with chronic renal disorder and disrupted metabolism of erythropoietin in ICR-derived glomerulonephritis (ICGN) mice. J Vet Med Sci. 2004;66(4):423–431.
  • Harris ZL, Durley AP, Man TK, et al. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci USA. 1999;96(19):10812–10817.
  • Ganz T, Nemeth E. Iron balance and the role of hepcidin in chronic kidney disease. Sem Nephrol. 2016;36(2):87–93.
  • Li H, Chen Z, Chen W, et al. MicroRNA-23b-3p deletion induces an IgA nephropathy-like disease associated with dysregulated mucosal IgA synthesis. JASN. 2021;32(10):2561–2578.
  • Abbad L, Monteiro RC, Berthelot L. Food antigens and transglutaminase 2 in IgA nephropathy: molecular links between gut and kidney. Mol Immunol. 2020;121:1–6.
  • Gesualdo L, Di Leo V, Coppo R. The mucosal immune system and IgA nephropathy. Semin Immunopathol. 2021;43(5):657–668.
  • Wu C‐Y, Hua K‐F, Yang S‐R, et al. Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1- and SIRT3-mediated autophagy induction. J Cell Mol Med. 2020;24(23):13609–13622.
  • Wu MY, Chen CS, Yiang GT, et al. The emerging role of pathogenesis of IgA nephropathy. J Clin Med. 2018;7(8):225.
  • Rauen T, Floege J. Inflammation in IgA nephropathy. Pediatr Nephrol. 2017;32(12):2215–2224.
  • Lai KN, Tang SCW, Guh J-Y, et al. Polymeric IgA1 from patients with IgA nephropathy upregulates transforming growth factor-beta synthesis and signal transduction in human mesangial cells via the renin-angiotensin system. J Am Soc Nephrol. 2003;14(12):3127–3137.
  • Lemley KV, Lafayette RA, Safai M, et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61(4):1475–1485.
  • Moriyama T. Clinical and histological features and therapeutic strategies for IgA nephropathy. Clin Exp Nephrol. 2019;23(9):1089–1099.
  • Schneider C, Owen MJ, Banville D, et al. Primary structure of human transferrin receptor deduced from the mRNA sequence. Nature. 1984;311(5987):675–678.
  • Gao G, Li J, Zhang Y, et al. Cellular iron metabolism and regulation. Adv Exp Med Biol. 2019;1173:21–32.
  • Wieland E, Shipkova M. Lymphocyte surface molecules as immune activation biomarkers. Clin Biochem. 2016;49(4-5):347–354.
  • Kawabata H, Yang R, Hirama T, et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem. 1999;274(30):20826–20832.
  • Kawabata H. Transferrin and transferrin receptors update. Free Rad Biol Med. 2019;133:46–54.
  • Moura IC, Centelles MN, Arcos-Fajardo M, et al. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J Exp Med. 2001;194(4):417–426.
  • Haddad E, Moura IC, Arcos-Fajardo M, et al. Enhanced expression of the CD71 mesangial IgA1 receptor in berger disease and Henoch-Schönlein nephritis: association between CD71 expression and IgA deposits. J Am Soc Nephrol. 2003;14(2):327–337.
  • Jhee JH, Nam BY, Park JT, et al. CD71 mesangial IgA1 receptor and the progression of IgA nephropathy. Transl Res. 2021;230:34–43.
  • Berthelot L, Papista C, Maciel TT, et al. Transglutaminase is essential for IgA nephropathy development acting through IgA receptors. J Exp Med. 2012;209(4):793–806.
  • Molyneux K, Wimbury D, Pawluczyk I, et al. β1,4-galactosyltransferase 1 is a novel receptor for IgA in human mesangial cells. Kidney Inter. 2017;92(6):1458–1468.
  • Feng H, Schorpp K, Jin J, et al. Transferrin receptor is a specific ferroptosis marker. Cell Reports. 2020;30(10):3411–3423.e7.
  • Speeckaert MM, Speeckaert R, Delanghe JR. Biological and clinical aspects of soluble transferrin receptor. Critic Rev Clin Laborat Sci. 2010;47(5-6):213–228.
  • Neef V, Schmitt E, Bader P, et al. The reticulocyte hemoglobin equivalent as a screening marker for iron deficiency and iron deficiency anemia in children. JCM. 2021;10(16):3506.
  • Ponikowska B, Suchocki T, Paleczny B, et al. Iron status and survival in diabetic patients with coronary artery disease. Diabetes Care. 2013;36(12):4147–4156.
  • Sierpinski R, Josiak K, Suchocki T, et al. High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality. Euro J Heart Fail. 2021;23(6):919–932.
  • Tański W, et al. Iron metabolism in patients with rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2021;25(12):4325–4335.
  • Rodríguez-Mortera R, et al. Higher hepcidin levels in adolescents with obesity are associated with metabolic syndrome dyslipidemia and visceral fat. Antioxidants. 2021;10(5):751.
  • Hameed S, et al. Is iron deficiency a risk factor for postpartum depression? A Case-Control study in the Gaza Strip, palestine. Public Health Nutr. 2022;25(6):1631 –1638.
  • Stojkovic Lalosevic M, Toncev L, Stankovic S, et al. Hepcidin is a reliable marker of iron deficiency anemia in newly diagnosed patients with inflammatory bowel disease. Dis Markers. 2020;2020:8523205.
  • He L, Liu H, Peng Y. [Immune pathogenesis of IgA nephropathy and its drugable targets]. zhong nan da xue xue bao. Yi xue ban = journal of Central South university. Med Sci. 2014;39(1):96–101.
  • Baker EN, Baker HM, Kidd RD. Lactoferrin and transferrin: functional variations on a common structural framework. Biochem Cell Biol. 2002;80(1):27–34.
  • Koshimura J, Narita T, Sasaki H, et al. Urinary excretion of transferrin and orosomucoid are increased after acute protein loading in healthy subjects. Nephron Clin Pract. 2005;100(2):c33–c37.
  • Bernard AM, Amor AA, Goemaere-Vanneste J, et al. Microtransferrinuria is a more sensitive indicator of early glomerular damage in diabetes than microalbuminuria. Clin Chem. 1988;34(9):1920–1921.
  • Li Y, Wang J, Zhu X, et al. Urinary protein markers predict the severity of renal histological lesions in children with mesangial proliferative glomerulonephritis. BMC Nephrol. 2012;13(1):29.
  • Sánchez-Hidalgo JJ, Suárez-Cuenca JA, Lozano-Nuevo JJ, et al. Urine transferrin as an early endothelial dysfunction marker in type 2 diabetic patients without nephropathy: a case control study. Diabetol Metab Syndr. 2021;13(1):128.
  • Sa-Li LI, Qiu-Ling FAN, Jie ZHAO, et al. Risk factors and correlation analysis between the oxford classification and clinical indicators of IgA nephropathy. J China Med Univ. 2017;46(1):1–6.
  • Agarwal AK, Yee J. Hepcidin. Adv Chronic Kidney Dis. 2019;26(4):298–305.
  • Nicolas G, Viatte L, Bennoun M, et al. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis. 2002;29(3):327–335.
  • Houamel D, Ducrot N, Lefebvre T, et al. Hepcidin as a major component of renal antibacterial defenses against uropathogenic Escherichia coli. J Am Soc Nephrol. 2016;27(3):835–846.
  • van Swelm RP, Wetzels JF, Verweij VG, et al. Renal handling of circulating and Renal-Synthesized hepcidin and its protective effects against Hemoglobin-Mediated kidney injury. JASN. 2016;27(9):2720–2732.
  • Mohammad G, Matakidou A, Robbins PA, et al. The kidney hepcidin/ferroportin axis controls iron reabsorption and determines the magnitude of kidney and systemic iron overload. Kidney Inter. 2021;100(3):559–569.
  • van Swelm RPL, Vos M, Verhoeven F, et al. Endogenous hepcidin synthesis protects the distal nephron against hemin and hemoglobin mediated necroptosis. Cell Death Dis. 2018;9(5):550.
  • Agarwal AK. Iron metabolism and management: focus on chronic kidney disease. Kidney Inter Suppl. 2021;11(1):46–58.
  • Kanamori Y, Murakami M, Sugiyama M, et al. Interleukin-1β (IL-1β) transcriptionally activates hepcidin by inducing CCAAT enhancer-binding protein δ (C/EBPδ) expression in hepatocytes. J Biol Chem. 2017;292(24):10275–10287.
  • Chen S, Feng T, Vujić Spasić M, et al. Transforming growth factor β1 (TGF-β1) activates hepcidin mRNA expression in hepatocytes. J Biol Chem. 2016;291(25):13160–13174.
  • Canali S, Core AB, Zumbrennen-Bullough KB, et al. Activin B induces noncanonical SMAD1/5/8 signaling via BMP type I receptors in hepatocytes: evidence for a role in hepcidin induction by inflammation in male mice. Endocrinology. 2016;157(3):1146–1162.
  • Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood. 2006;108(9):3204–3209.
  • Yu G-Z, Guo L, Dong J-F, et al. Persistent hematuria and kidney disease progression in IgA nephropathy: a cohort study. Am J Kidney Dis. 2020;76(1):90–99.
  • Sevillano AM, Gutiérrez E, Yuste C, et al. Remission of hematuria improves renal survival in IgA nephropathy. JASN. 2017;28(10):3089–3099.
  • Gammella E, Buratti P, Cairo G, et al. The transferrin receptor: the cellular iron gate. Metallomics Integrated Biometal Sci. 2017;9(10):1367–1375.
  • Wang W, Di X, D'Agostino RB, et al. Excess capacity of the iron regulatory protein system. J Biol Chem. 2007;282(34):24650–24659.
  • Batista A, Millán J, Mittelbrunn M, et al. Recruitment of transferrin receptor to immunological synapse in response to TCR engagement. J Immunol. 2004;172(11):6709–6714.
  • Jabara HH, Boyden SE, Chou J, et al. A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat Genet. 2016;48(1):74–78.
  • Senyilmaz D, Virtue S, Xu X, et al. Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature. 2015;525(7567):124–128.
  • Zeltina A, Krumm SA, Sahin M, et al. Convergent immunological solutions to argentine hemorrhagic fever virus neutralization. Proc Natl Acad Sci USA. 2017;114(27):7031–7036.
  • Pagani A, Vieillevoye M, Nai A, et al. Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form. Haematologica. 2015;100(4):458–465.
  • Graham RM, Reutens GM, Herbison CE, et al. Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron. J Hepatol. 2008;48(2):327–334.
  • Yin P, Song Y, Li J. Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing high-flux hemodialysis. Bosn J of Basic Med Sci. 2017;17(4):333–338.
  • McKnight GS, Lee DC, Hemmaplardh D, et al. Transferrin gene expression. Effects of nutritional iron deficiency. J Biol Chem. 1980;255(1):144–147.
  • Zhao L, Zou Y, Zhang J, et al. Serum transferrin predicts end-stage renal disease in type 2 diabetes mellitus patients. Int J Med Sci. 2020;17(14):2113–2124.
  • Krause A, Neitz S, Mägert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000;480(2-3):147–150.
  • Qiao B, Sugianto P, Fung E, et al. Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab. 2012;15(6):918–924.
  • Aschemeyer S, Qiao B, Stefanova D, et al. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood. 2018;131(8):899–910.
  • Park CH, Valore EV, Waring AJ, et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806–7810.
  • Moulouel B, Houamel D, Delaby C, et al. Hepcidin regulates intrarenal iron handling at the distal nephron. Kidney Inter. 2013;84(4):756–766.
  • Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631–1634.
  • Ueda N, Takasawa K. Impact of inflammation on ferritin, hepcidin and the management of iron deficiency anemia in chronic kidney disease. Nutrients. 2018;10(9):1173.
  • Sutherland M, Shankaranarayanan P, Schewe T, et al. Evidence for the presence of phospholipid hydroperoxide glutathione peroxidase in human platelets: implications for its involvement in the regulatory network of the 12-lipoxygenase pathway of arachidonic acid metabolism. Biochem J. 2001;353(1):91–100.
  • Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1-2):317–331.
  • Zhang J, Bi J, Ren Y, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol. 2021;236(2):931–945.
  • Yuan Y, Zhai Y, Chen J, et al. Kaempferol ameliorates Oxygen-Glucose deprivation/Reoxygenation-Induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis. Biomolecules. 2021;11(7):923.
  • Mayr L, Grabherr F, Schwärzler J, et al. Dietary lipids fuel GPX4-restricted enteritis resembling crohn’s disease. Nat Commun. 2020;11(1):1775.
  • Capelletti MM, Manceau H, Puy H, et al. Ferroptosis in liver diseases: an overview. IJMS. 2020;21(14):4908.
  • Forcina GC, Dixon SJ. GPX4 at the crossroads of lipid homeostasis and ferroptosis. Proteomics. 2019;19(18):e1800311.
  • Hu Z, Zhang H, Yi B, et al. VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell Death Dis. 2020;11(1):73.
  • Zhang X, Li LX, Ding H, et al. Ferroptosis promotes cyst growth in autosomal dominant polycystic kidney disease mouse models. JASN. 2021;32(11):2759–2776.
  • Kim S, Kang S-W, Joo J, et al. Characterization of ferroptosis in kidney tubular cell death under diabetic conditions. Cell Death Dis. 2021;12(2):160.
  • Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50(1):323–354.
  • Ferrándiz ML, Devesa I. Inducers of heme oxygenase-1. CPD. 2008;14(5):473–486.
  • Chin HJ, et al. The heme oxygenase-1 genotype is a risk factor to renal impairment of IgA nephropathy at diagnosis, which is a strong predictor of mortality. J Korean Med Sci. 2009;24 Suppl(Suppl 1):S30–S37.
  • Tang D, Kang R, Berghe TV, et al. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347–364.
  • Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072.
  • Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016;73(11-12):2195–2209.
  • Yang WS, et al. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA. 2016;113(34):E4966–E4975.
  • Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol. 2017;13(1):81–90.
  • Ursini F, Maiorino M. Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Rad Biol Med. 2020;152:175–185.
  • Wang H, Nishiya K, Ito H, et al. Iron deposition in renal biopsy specimens from patients with kidney diseases. Am J Kidney Dis. 2001;38(5):1038–1044.
  • Taguchi S, Hidaka S, Yanai M, et al. Renal hemosiderosis presenting with acute kidney injury and macroscopic hematuria in immunoglobulin a nephropathy: a case report. BMC Nephrol. 2021;22(1):132.
  • Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges. Anal Biochem. 2017;524:13–30.
  • Tian J, et al. Lipid peroxidation in IgA nephropathy and the effect of lipo-prostaglandin E1. J Nephrol. 2005;18(3):243–248.
  • Ya-Jun BAI, Yan-bin DU, Xin-Zhu YUAN, et al. Regulation of chrysophanol-mediated TLR4/NF-κB pathway on renal injury and immune response in IgA nephropathy rats. Sichuan Da Xue Xue Bao Yi Xue Ban. 2019;50(6):840–846.
  • Zhang H-L, Hu B-X, Li Z-L, et al. PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis. Nat Cell Biol. 2022;24(1):88–98.
  • Wang Y, Quan F, Cao Q, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2021;28:231–243.
  • Mishima E, Ito J, Wu Z, et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature. 2022;608(7924):778–783.
  • Shao C, Yuan J, Liu Y, et al. Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis. Proc Natl Acad Sci USA. 2020;117(19):10155–10164.
  • Trakshel GM, Kutty RK, Maines MD. Purification and characterization of the major constitutive form of testicular heme oxygenase. The noninducible isoform. J Biol Chem. 1986;261(24):11131–11137.
  • Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem. 1986;261(1):411–419.
  • Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37:517–554.
  • Maines MD, Kappas A. Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity. Proc Natl Acad Sci USA. 1974;71(11):4293–4297.
  • Korolnek T, Hamza I. Macrophages and iron trafficking at the birth and death of red cells. Blood. 2015;125(19):2893–2897.
  • Theurl I, Hilgendorf I, Nairz M, et al. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat Med. 2016;22(8):945–951.
  • Applegate LA, Luscher P, Tyrrell RM. Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. Cancer Res. 1991;51(3):974–978.
  • Shepard M, Dhulipala P, Kabaria S, et al. Heme oxygenase-1 localization in the rat nephron. Nephron. 2002;92(3):660–664.
  • Suzuki K. Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules. 2019;9(6):223.
  • Weiss U. Inflammation. Nature. 2008;454(7203):427.
  • Kitching AR, Hutton HL. The players: cells involved in glomerular disease. CJASN. 2016;11(9):1664–1674.
  • Lai KN, Leung JCK, Chan LYY, et al. Activation of podocytes by mesangial-derived TNF-alpha: glomerulo-podocytic communication in IgA nephropathy. Am J Physiol Renal Physiol. 2008;294(4):F945–F955.
  • Groza Y, Jemelkova J, Kafkova LR, et al. IL-6 and its role in IgA nephropathy development. Cytokine Growth Factor Rev. 2022;66:1–14.
  • Liang Y, Zhao G, Tang L, et al. MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients. Exp Cell Res. 2016;347(2):312–321.
  • Zhang Y, Yan X, Zhao T, et al. Targeting C3a/C5a receptors inhibits human mesangial cell proliferation and alleviates immunoglobulin a nephropathy in mice. Clin Experim Immunol. 2017;189(1):60–70.
  • Stenvinkel P, Chertow GM, Devarajan P, et al. Chronic inflammation in chronic kidney disease progression: role of Nrf2. Kidney Inter Rep. 2021;6(7):1775–1787.
  • Lai KN, et al. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrology, dialysis, transplantation: official publication of the european dialysis and transplant association. Euro Renal Assoc. 2009;24(1):62–72.
  • Chan LY, Leung JC, Tsang AW, et al. Activation of tubular epithelial cells by mesangial-derived TNF-alpha: glomerulotubular communication in IgA nephropathy. Kidney Inter. 2005;67(2):602–612.
  • Tang R, Meng T, Lin W, et al. A partial picture of the Single-Cell transcriptomics of human IgA nephropathy. Front Immunol. 2021;12:645988.
  • Zambrano S, He L, Kano T, et al. Molecular insights into the early stage of glomerular injury in IgA nephropathy using single-cell RNA sequencing. Kidney Inter. 2022;101(4):752–765.
  • Moura IC, Benhamou M, Launay P, et al. The glomerular response to IgA deposition in IgA nephropathy. Sem Nephrol. 2008;28(1):88–95.
  • Ricchi P, Meloni A, Costantini S, et al. Soluble form of transferrin receptor-1 level is associated with the age at first diagnosis and the risk of therapeutic intervention and iron overloading in patients with non-transfusion-dependent thalassemia. Ann Hematol. 2017;96(9):1541–1546.
  • Guang-Zhi Z, Peng-Fei , HU. The correlation of serum hepcidin and transferrin receptor contents with iron deficiency and micro-inflammatory response in patients with hemodialysis. J Hainan Med Univ. 2018;24(1):30–33. in Chinese).
  • Brandsma ME, Jevnikar AM, Ma S. Recombinant human transferrin: beyond iron binding and transport. Biotechnol Adv. 2011;29(2):230–238.
  • De Puysseleyr L, De Puysseleyr K, Rybarczyk J, et al. Transferrins reduce replication of in McCoy cells. Pathogens. 2021;10(7):858.
  • Claise C, et al. Low transferrin levels predict heightened inflammation in COVID-19 patients: new insights. Inter J Infect Dis. 2021;116:74–79.
  • Hui PENG, Xue-Qing YU, Tan-Qi LOU, et al. Correlation between urinary protein components and renal pathology in primary glomerulonephritis patients of different pathological types. Chin J Nephrol. 2006;22(5):271–274.
  • Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110(7):1037–1044.
  • Diepeveen LE, Stegemann G, Wiegerinck ET, et al. Investigating the molecular mechanisms of renal hepcidin induction and protection upon Hemoglobin-Induced acute kidney injury. IJMS. 2022;23(3):1352.
  • Scindia Y, Wlazlo E, Leeds J, et al. Protective role of hepcidin in polymicrobial sepsis and acute kidney injury. Front Pharmacol. 2019;10:615.
  • Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–2093.
  • Ranieri E, Gesualdo L, Petrarulo F, et al. Urinary IL-6/EGF ratio: a useful prognostic marker for the progression of renal damage in IgA nephropathy. Kidney Int. 1996;50(6):1990–2001.
  • Kayama F, Yoshida T, Elwell MR, et al. Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration. Toxicol Appl Pharmacol. 1995;134(1):26–34.
  • Sun Y, Chen P, Zhai B, et al. The emerging role of ferroptosis in inflammation. Biomed Pharmacother Biomed Pharmacother. 2020;127:110108.
  • Campbell NK, Fitzgerald HK, Dunne A. Regulation of inflammation by the antioxidant haem oxygenase 1. Nat Rev Immunol. 2021;21(7):411–425.
  • Naito Y, Takagi T, Higashimura Y. Heme oxygenase-1 and anti-inflammatory M2 macrophages. Arch Biochem Biophys. 2014;564:83–88.
  • Waltz P, Carchman EH, Young AC, et al. Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy. 2011;7(3):315–320.
  • Hull TD, Agarwal A, George JF. The mononuclear phagocyte system in homeostasis and disease: a role for heme oxygenase-1. Antioxid Redox Signal. 2014;20(11):1770–1788.
  • Orozco LD, Kapturczak MH, Barajas B, et al. Heme oxygenase-1 expression in macrophages plays a beneficial role in atherosclerosis. Circul Res. 2007;100(12):1703–1711.
  • Zhang M, Nakamura K, Kageyama S, et al. Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury. JCI Insight. 2018;3(19):e120596.
  • Morimoto K, Ohta K, Yachie A, et al. Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases. Kidney Int. 2001;60(5):1858–1866.
  • Kimura S, Aung NY, Ohe R, et al. Increasing heme oxygenase-1-Expressing macrophages indicates a tendency of poor prognosis in advanced colorectal cancer. Digestion. 2020;101(4):401–410.
  • Jais A, Einwallner E, Sharif O, et al. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell. 2014;158(1):25–40.
  • Carasi P, Rodríguez E, da Costa V, et al. Heme-Oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection. Front Immunol. 2017;8:883.
  • Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical practice guideline for the management of glomerular diseases. Kidney Inter, 2021;100(4S):S1–S276.
  • Preza GC, Ruchala P, Pinon R, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest. 2011;121(12):4880–4888.
  • Sasu BJ, Cooke KS, Arvedson TL, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010;115(17):3616–3624.
  • Jing W, Nunes ACF, Farzaneh T, et al. Phosphate binder, ferric citrate, attenuates anemia, renal dysfunction, oxidative stress, inflammation, and fibrosis in 5/6 nephrectomized CKD rats. J Pharmacol Exp Ther. 2018;367(1):129–137.
  • Paller MS, Hedlund BE, Sikora JJ, et al. Role of iron in postischemic renal injury in the rat. Kidney Inter. 1988;34(4):474–480.
  • Rajapurkar MM, Hegde U, Bhattacharya A, et al. Effect of deferiprone, an oral iron chelator, in diabetic and non-diabetic glomerular disease. Toxicol Mech Methods. 2013;23(1):5–10.
  • Bloomer SA, Brown KE, Buettner GR, et al. Dysregulation of hepatic iron with aging: implications for heat stress-induced oxidative liver injury. Am J Physiol Regulat Integr Compar Physiol. 2008;294(4):R1165–R1174.
  • Bloomer SA, Brown KE, Kregel KC. Renal iron accumulation and oxidative injury with aging: effects of treatment with an iron chelator. J Gerontol Series A Biol Sci Med Sci. 2020;75(4):680–684.
  • Ramagiri S, Pan S, DeFreitas D, et al. Deferoxamine prevents neonatal posthemorrhagic hydrocephalus through choroid Plexus-Mediated iron clearance. Transl Stroke Res. 2022.