{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:57:38Z","timestamp":1779379058611,"version":"3.53.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ORKID"},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00c3\u00a9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010431","name":"IMEA","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010431","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018737","name":"LabEx Inflamex","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018737","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background and hypothesis<\/jats:title>\n<jats:p>IgA nephropathy (IgAN) is the most common glomerulonephritis and major cause of renal failure worldwide. Its pathogenesis involves galactose deficient IgA1-immune complexes containing soluble IgA Fc receptor (sCD89). Both IgA1 and sCD89 bind independently to the transferrin receptor (TfR1, CD71), a mesangial IgA1 receptor. Here, we hypothesize that sCD89 plays a pathogenic role in IgAN by driving a tri-partite IgA1-sCD89-CD71 complex inducing activation <jats:italic><jats:italic>in situ<\/jats:italic><\/jats:italic> of the mTOR (mammalian target of rapamycin) signaling pathway in mesangial cells and contributing to disease progression. mTOR inhibition may disrupt this pathogenic axis, reducing IgA1 and sCD89 deposits, modulating CD71 expression, and alleviating disease manifestations. Here, we investigated the role of sCD89 and a mTOR inhibitor using humanized mouse models of IgAN expressing CD89 and\/or IgA1.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Single cell and RNAseq data were obtained from public IgAN dataset and immunostaining was performed on childhood IgAN (cIgAN) biopsies. Human mesangial cells (HMCs) stimulation by recombinant sCD89 (rsCD89) was followed by western blot analysis. Pre-clinical assays with mTOR inhibitor (Everolimus) by oral gavage were performed using young \u03b11<jats:sup>KI<\/jats:sup> mice injected with rsCD89 for 25 days (preventive protocol) and adult \u03b11<jats:sup>KI<\/jats:sup>CD89<jats:sup>Tg<\/jats:sup> mice (treated protocol) for 75 days. Proteinuria, renal function, and circulating immune complexes (CICs) were analyzed and kidneys were harvested for histology.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>RNAseq revealed increased TfR1 and mTOR expression in mesangial cells from IgAN patients. TfR1 upregulation was confirmed in cIgAN biopsies. sCD89 stimulation induced HMC TfR1 expression and phosphorylation of mTOR, Akt and S6K1. Everolimus treatment prevented or reverted mesangial IgA1 and C3 deposits and also decreased mesangial TfR1 and cell proliferation. Everolimus impaired levels of sCD89- and IgA-CIC, proteinuria, as well as renal function.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These findings highlight the critical role of the sCD89-TfR1-mTOR axis in IgAN pathogenesis and support the use of mTOR inhibitors as a novel therapeutic approach. This approach could significantly improve outcomes by slowing disease progression and minimizing the systemic toxic effects of current immunosuppressive therapies. This is particularly crucial for pediatric patients, where the only approved treatment \u2013 steroids \u2013 has severe side effects, including detrimental impacts on bone health and growth.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318581","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T17:32:37Z","timestamp":1759858357000},"page":"e0318581","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Blockade of mTOR ameliorates IgA nephropathy by correcting CD89 and CD71 dysfunctions in humanized mice"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-1456","authenticated-orcid":true,"given":"Alexandra","family":"Cambier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Canesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lison Lachize","family":"Neanne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Sannier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-4077","authenticated-orcid":true,"given":"H\u00e9l\u00e8ne","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Boedec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Badie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato C.","family":"Monteiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"1","key":"pone.0318581.ref001","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41581-024-00885-3","article-title":"The pathogenesis of IgA nephropathy and implications for treatment","volume":"21","author":"CK Cheung","year":"2025","journal-title":"Nat Rev Nephrol"},{"issue":"7","key":"pone.0318581.ref002","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/s41588-023-01422-x","article-title":"Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy","volume":"55","author":"K Kiryluk","year":"2023","journal-title":"Nat Genet"},{"issue":"7","key":"pone.0318581.ref003","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1681\/ASN.2016091043","article-title":"Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1","volume":"28","author":"DP Gale","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"pone.0318581.ref004","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1471-2369-5-10","article-title":"Race\/ethnicity and disease severity in IgA nephropathy","volume":"5","author":"YN Hall","year":"2004","journal-title":"BMC Nephrol"},{"issue":"4","key":"pone.0318581.ref005","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/S0272-6386(97)90333-4","article-title":"Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases","volume":"29","author":"A Koyama","year":"1997","journal-title":"Am J Kidney Dis"},{"issue":"10032","key":"pone.0318581.ref006","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/S0140-6736(16)00272-5","article-title":"Primary glomerulonephritides","volume":"387","author":"J Floege","year":"2016","journal-title":"Lancet"},{"issue":"4","key":"pone.0318581.ref007","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.ekir.2018.03.013","article-title":"Immunosuppressive Treatment in Children With IgA Nephropathy and the Clinical Value of Podocytopathic Features","volume":"3","author":"A Cambier","year":"2018","journal-title":"Kidney Int Rep"},{"issue":"2","key":"pone.0318581.ref008","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1681\/ASN.V82199","article-title":"Predicting renal outcome in IgA nephropathy","volume":"8","author":"MG Radford","year":"1997","journal-title":"J Am Soc Nephrol"},{"issue":"8","key":"pone.0318581.ref009","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.2215\/CJN.00910121","article-title":"Recurrence of IgA Nephropathy after Kidney Transplantation in Adults","volume":"16","author":"A Uffing","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"issue":"5","key":"pone.0318581.ref010","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00281-021-00883-8","article-title":"IgA glycosylation and immune complex formation in IgAN","volume":"43","author":"H Suzuki","year":"2021","journal-title":"Semin Immunopathol"},{"issue":"740","key":"pone.0318581.ref011","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adl6149","article-title":"The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis","volume":"16","author":"PJ Gleeson","year":"2024","journal-title":"Sci Transl Med"},{"key":"pone.0318581.ref012","doi-asserted-by":"crossref","first-page":"1165394","DOI":"10.3389\/fimmu.2023.1165394","article-title":"Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy","volume":"14","author":"Y Nihei","year":"2023","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0318581.ref013","doi-asserted-by":"crossref","first-page":"5806","DOI":"10.4049\/jimmunol.163.11.5806","article-title":"Crosslinking of the human Fc receptor for IgA (FcalphaRI\/CD89) triggers FcR gamma-chain-dependent shedding of soluble CD89","volume":"163","author":"G van Zandbergen","year":"1999","journal-title":"J Immunol"},{"issue":"11","key":"pone.0318581.ref014","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1084\/jem.191.11.1999","article-title":"Fcalpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger\u2019s disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice","volume":"191","author":"P Launay","year":"2000","journal-title":"J Exp Med"},{"issue":"1","key":"pone.0318581.ref015","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1365-2567.2009.03215.x","article-title":"Ectodomain shedding of Fcalpha receptor is mediated by ADAM10 and ADAM17","volume":"130","author":"M Peng","year":"2010","journal-title":"Immunology"},{"issue":"5","key":"pone.0318581.ref016","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1046\/j.1523-1755.1998.00885.x","article-title":"Down-regulation of Fc alpha receptors on blood cells of IgA nephropathy patients: evidence for a negative regulatory role of serum IgA","volume":"53","author":"B Grosset\u00eate","year":"1998","journal-title":"Kidney Int"},{"issue":"12","key":"pone.0318581.ref017","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.molmed.2015.10.003","article-title":"Molecular Insights into the Pathogenesis of IgA Nephropathy","volume":"21","author":"T Robert","year":"2015","journal-title":"Trends Mol Med"},{"issue":"9","key":"pone.0318581.ref018","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1681\/ASN.2012010053","article-title":"Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy","volume":"23","author":"F Berthoux","year":"2012","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"pone.0318581.ref019","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/ki.2015.158","article-title":"Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes","volume":"88","author":"L Berthelot","year":"2015","journal-title":"Kidney Int"},{"issue":"10","key":"pone.0318581.ref020","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1681\/ASN.2018111156","article-title":"Glomerular Immunodeposits of Patients with IgA Nephropathy Are Enriched for IgG Autoantibodies Specific for Galactose-Deficient IgA1","volume":"30","author":"DV Rizk","year":"2019","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"pone.0318581.ref021","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.kint.2021.09.023","article-title":"Soluble CD89 is a critical factor for mesangial proliferation in childhood IgA nephropathy","volume":"101","author":"A Cambier","year":"2022","journal-title":"Kidney Int"},{"key":"pone.0318581.ref022","doi-asserted-by":"crossref","first-page":"1128393","DOI":"10.3389\/fmed.2023.1128393","article-title":"Molecular insight in intrarenal inflammation affecting four main types of cells in nephrons in IgA nephropathy","volume":"10","author":"H Zhang","year":"2023","journal-title":"Front Med (Lausanne)"},{"issue":"5","key":"pone.0318581.ref023","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.semnephrol.2018.05.018","article-title":"Role of Mesangial-Podocytic-Tubular Cross-Talk in IgA Nephropathy","volume":"38","author":"JCK Leung","year":"2018","journal-title":"Semin Nephrol"},{"issue":"3","key":"pone.0318581.ref024","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1159\/000514183","article-title":"Role of Human Mesangial-Tubular Crosstalk in Secretory IgA-Induced IgA Nephropathy","volume":"46","author":"J Zhang","year":"2021","journal-title":"Kidney Blood Press Res"},{"issue":"5","key":"pone.0318581.ref025","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.kint.2017.02.003","article-title":"Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group","volume":"91","author":"H Trimarchi","year":"2017","journal-title":"Kidney Int"},{"issue":"4","key":"pone.0318581.ref026","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1084\/jem.194.4.417","article-title":"Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy","volume":"194","author":"IC Moura","year":"2001","journal-title":"J Exp Med"},{"issue":"1","key":"pone.0318581.ref027","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1084\/jem.20071204","article-title":"Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease","volume":"205","author":"T Matysiak-Budnik","year":"2008","journal-title":"J Exp Med"},{"issue":"2","key":"pone.0318581.ref028","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/01.ASN.0000046961.04917.83","article-title":"Enhanced expression of the CD71 mesangial IgA1 receptor in Berger disease and Henoch-Sch\u00f6nlein nephritis: association between CD71 expression and IgA deposits","volume":"14","author":"E Haddad","year":"2003","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"pone.0318581.ref029","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1097\/01.ASN.0000115401.07980.0C","article-title":"Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy","volume":"15","author":"IC Moura","year":"2004","journal-title":"J Am Soc Nephrol"},{"issue":"9","key":"pone.0318581.ref030","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1681\/ASN.2004111006","article-title":"Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy","volume":"16","author":"IC Moura","year":"2005","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"pone.0318581.ref031","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.20112005","article-title":"Transglutaminase is essential for IgA nephropathy development acting through IgA receptors","volume":"209","author":"L Berthelot","year":"2012","journal-title":"J Exp Med"},{"issue":"12","key":"pone.0318581.ref032","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ki.2012.192","article-title":"The IgA1 immune complex-mediated activation of the MAPK\/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy","volume":"82","author":"H Tamouza","year":"2012","journal-title":"Kidney Int"},{"issue":"6","key":"pone.0318581.ref033","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation","volume":"36","author":"MC Mendoza","year":"2011","journal-title":"Trends Biochem Sci"},{"issue":"2","key":"pone.0318581.ref034","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"M Laplante","year":"2012","journal-title":"Cell"},{"issue":"11","key":"pone.0318581.ref035","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1016\/j.clinthera.2017.09.011","article-title":"Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review","volume":"39","author":"JB Rice","year":"2017","journal-title":"Clin Ther"},{"issue":"7","key":"pone.0318581.ref036","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1073\/pnas.0912393107","article-title":"Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation","volume":"107","author":"S Duchez","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0318581.ref037","doi-asserted-by":"crossref","first-page":"645988","DOI":"10.3389\/fimmu.2021.645988","article-title":"A Partial Picture of the Single-Cell Transcriptomics of Human IgA Nephropathy","volume":"12","author":"R Tang","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0318581.ref038","doi-asserted-by":"crossref","first-page":"873923","DOI":"10.3389\/fmed.2022.873923","article-title":"Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments","volume":"9","author":"AM Raghubar","year":"2022","journal-title":"Front Med (Lausanne)"},{"issue":"7","key":"pone.0318581.ref039","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41419-022-05081-4","article-title":"Beyond controlling cell size: functional analyses of S6K in tumorigenesis","volume":"13","author":"X Wu","year":"2022","journal-title":"Cell Death Dis"},{"key":"pone.0318581.ref040","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/nep.14344","article-title":"Closing remarks from the IIGANN2023 Tokyo symposium-40\u2009years of study progress in IgA nephropathy","author":"RC Monteiro","year":"2024","journal-title":"Nephrology (Carlton)"},{"issue":"12","key":"pone.0318581.ref041","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.ekir.2023.09.024","article-title":"Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy","volume":"8","author":"FWK Tam","year":"2023","journal-title":"Kidney Int Rep"},{"key":"pone.0318581.ref042","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.immunol.21.120601.141011","article-title":"IgA Fc receptors","volume":"21","author":"RC Monteiro","year":"2003","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"pone.0318581.ref043","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/imr.13424","article-title":"Immunoglobulin a antibodies: from protection to harmful roles","volume":"328","author":"PJ Gleeson","year":"2024","journal-title":"Immunol Rev"},{"issue":"1","key":"pone.0318581.ref044","first-page":"31","article-title":"Identification of FcalphaRI as an inhibitory receptor that controls inflammation: dual role of FcRgamma ITAM","volume":"22","author":"B Pasquier","year":"2005","journal-title":"Immunity"},{"issue":"7","key":"pone.0318581.ref045","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1002\/art.39142","article-title":"Reversal of Arthritis by Human Monomeric IgA Through the Receptor-Mediated SH2 Domain-Containing Phosphatase 1 Inhibitory Pathway","volume":"67","author":"E Rossato","year":"2015","journal-title":"Arthritis Rheumatol"},{"issue":"11","key":"pone.0318581.ref046","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1093\/ndt\/gfr448","article-title":"IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells","volume":"26","author":"J Novak","year":"2011","journal-title":"Nephrol Dial Transplant"},{"issue":"12","key":"pone.0318581.ref047","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/ki.2010.314","article-title":"Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy","volume":"78","author":"MT Vuong","year":"2010","journal-title":"Kidney Int"},{"issue":"12","key":"pone.0318581.ref048","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1093\/ndt\/13.12.3058","article-title":"Reduced binding of immunoglobulin A (IgA) from patients with primary IgA nephropathy to the myeloid IgA Fc-receptor, CD89","volume":"13","author":"G van Zandbergen","year":"1998","journal-title":"Nephrol Dial Transplant"},{"issue":"16","key":"pone.0318581.ref049","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.3390\/molecules27165295","article-title":"Overview of Research into mTOR Inhibitors","volume":"27","author":"B Mao","year":"2022","journal-title":"Molecules"},{"issue":"11","key":"pone.0318581.ref050","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.1093\/ndt\/gfr072","article-title":"Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy","volume":"26","author":"JM Cruzado","year":"2011","journal-title":"Nephrol Dial Transplant"},{"issue":"10","key":"pone.0318581.ref051","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1039\/C7MT00143F","article-title":"The transferrin receptor: the cellular iron gate","volume":"9","author":"E Gammella","year":"2017","journal-title":"Metallomics"},{"issue":"5","key":"pone.0318581.ref052","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.cmet.2012.10.001","article-title":"mTOR regulates cellular iron homeostasis through tristetraprolin","volume":"16","author":"M Bayeva","year":"2012","journal-title":"Cell Metab"},{"issue":"1","key":"pone.0318581.ref053","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/0886022X.2019.1577257","article-title":"The protective effect and mechanism of rapamycin in the rat model of IgA nephropathy","volume":"41","author":"N Guo","year":"2019","journal-title":"Ren Fail"},{"issue":"740","key":"pone.0318581.ref054","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adl6149","article-title":"The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis","volume":"16","author":"PJ Gleeson","year":"2024","journal-title":"Sci Transl Med"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0345118","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000}}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T17:32:46Z","timestamp":1759858366000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318581"}},"subtitle":[],"editor":[{"given":"Jingyu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":54,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0318581","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]}}}