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Diabetes nephropathy (DN) is the most significant microvascular complication of diabetes worldwide due to hyperglycemiainduced podocyte injury and apoptosis. The role of methyl CpG binding protein 2 (MECP2) has been observed, but its specific involvement in DN remains unclear. In this study, an in vitro DN model was established using human glomerular podocytes exposed to high glucose (HG, 30 mM). MECP2 expression was assessed using qRT-PCR and Western Blot. Proliferation and migration were evaluated through CCK-8 and transwell assays in both the HG group and the HG + MECP2 knockdown group. Apoptosis was assessed by flow cytometry and Western Blot. RNA-Sequencing identified differentially expressed genes (DEGs) between HG and HG+MECP2 knockdown groups, with subsequent enrichment analysis using KEGG and GSEA databases. Our results revealed elevated MECP2 expression in HG-treated podocytes compared to the control group. Podocytes with MECP2 knockdown displayed increased proliferation and migration compared to the HG group. MECP2 knockdown significantly inhibited HG-induced apoptosis in podocytes, with lower expression of pro-apoptotic protein (cleaved-caspase3, Bax, BAD, Desmin) and higher expression of anti-apoptotic protein Bcl-2 in the HG+MECP2 shRNA group. RNA sequencing identified 123 upregulated and 129 downregulated DEGs. Enrichment analysis highlighted apoptosis-related pathways like PPAR, TNF, p53, RELAXIN, WNT, and RAP1 signaling. Podocytes with MECP2 knockdown showed reduced apoptosis upon HG treatment. In summary, downregulation of MECP2 in podocytes effectively mitigated apoptosis caused by high glucose, suggesting a potential strategy to improve diabetes nephropathy outcomes.
Li et al. (Wed,) studied this question.