COL4A3 Mutation induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2
نویسندگان
چکیده
IntroductionPodocyte apoptosis is a common mechanism driving progression in Alport syndrome(AS). The aim of this study was to investigate the podocyte caused by COL4A3 mutations.MethodsWe recruited autosomal dominant AS(ADAS) patients. Patients with minimal change disease (MCD) were as controls. Microarray analysis carried out on isolated glomeruli from patients and validated. Then, corresponding mutant human podocytes(p.C1616Y) 129 mice(p.C1615Y, murine homolog p.C1616Y) constructed. highest differentially expressed genes (DEGs) microarray validated transgenic mice podocytes before after admnistration MMP-2 inhibitor(SB-3CT), NOX4 inhibitor(GKT137831). We further NOX4/MMP-2/apoptosis pathway real-time PCR, immunohistochemistry western blot renal tissue ADAS patients.ResultsUsing analysis, we observed that DEGs including NOX4/H2O2, apoptosis-related significantly upregulated. These histologic (p.C1616Y) and/or models (p.C1615Y). Moreover, found abrogated expression downregulated both vivo vitro inhibition, urinary albumin-to-creatinine ratio, 24 hour proteinuria pathologic lesion attenuated inhibition vivo; Furthermore, while remained same vitro.ConclusionThese results indicate might induce through regulation mutations. Our findings provided new insights into ADAS.
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ژورنال
عنوان ژورنال: Kidney International Reports
سال: 2023
ISSN: ['2468-0249']
DOI: https://doi.org/10.1016/j.ekir.2023.06.007