
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease, with unclear mechanisms. Using integrative transcriptome analysis of bulk and single-cell RNA datasets, this study identified Serpine2 as a key gene regulating the ‘collagen-containing extracellular matrix’ pathway in DN. Animal and cellular models showed Serpine2 upregulation in mesangial cells (MCs), contributing to excessive proliferation and extracellular matrix (ECM) accumulation. Knockdown experiments demonstrated that Serpine2 alleviates these effects, while ERK pathway activation (via Ro 67-7476) reversed this protection. These findings implicate Serpine2 in DN pathogenesis through ERK1/2 pathway activation, offering potential new therapeutic targets for glomerulosclerosis in DN progression.
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