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The novel involvement of podocyte autophagic activity in the pathogenesis of lupus nephritis

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dc.contributor.authorJin, Juan
dc.contributor.authorYe, Meiyu
dc.contributor.authorZhao, Li
dc.contributor.authorZou, Wenli
dc.contributor.authorShen, Wei
dc.contributor.authorZhang, Hongjuan
dc.contributor.authorGong, Jianguang
dc.contributor.authorHe, Qiang
dc.date.accessioned2022-05-12T06:29:24Z
dc.date.available2022-05-12T06:29:24Z
dc.date.issued2018
dc.description.abstractBackground. Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. Methods. Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated. Podocytes were observed by electron microscopy, and autophagic activity was evaluated by immunofluorescence staining and western blot analysis. Apoptotic activity was evaluated by immunohistochemistry, TUNEL assays and flow cytometric analysis. Results. Significantly greater podocyte injury and discrepant autophagic levels were observed in LN patients. Differentiated mouse podocytes in the LN group showed reduced nephrin expression and increased apoptosis, as well as significantly higher levels of apoptosis-related proteins (cleaved caspase-3 and Bax). In the mice LN group, the increased number of autophagosomes was accompanied by increased LC3- II/LC3-I ratios and decreased p62, suggesting increased autophagic and apoptotic activity in podocytes. Blockade of autophagic activity by 3-MA or siRNAmediated silencing of Atg5 resulted in decreases in LC3- II/LC3-I ratios, podocyte apoptosis and damage in the mice LN group. Futhermore, Rapamycin treatment increased LC3-II/LC3-I ratios, and enhanced LNinduced apoptosis in podocyte from modal animal. Conclusions. This study demonstrates that autophagic activity of podocytes is a crucial factor in renal injury by directly affecting the function of podocyte; thus, inhibiting this activity during the early stages of LN is implicated as a potential therapeutic strategy for delaying the progression of LN. Also, clinical application in LN needs to consider patients’ pathological type and drugs’ comprehensive effectiveness.es
dc.formatapplication/pdfes
dc.format.extent12es
dc.identifier.doiDOI: 10.14670HH-11-974
dc.identifier.eisbnHistology and Histopathology, Vol.33, nº8, (2018)es
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/119883
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectLupus nephritises
dc.subjectAutophagyes
dc.subjectPodocytees
dc.subjectApoptosises
dc.subjectRapamycines
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleThe novel involvement of podocyte autophagic activity in the pathogenesis of lupus nephritises
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.33, nº8 (2018)