Mesenchymal stem cells in diabetic kidney disease: Potential regulatory mechanisms and related signaling pathways of mesenchymal stem cells

Diabetic kidney disease (DKD) is a severe complication of diabetes and the leading cause of end-stage renal disease (ESRD). However, DKD treatment remains challenging owing to its complex etiology and unclear pathogenesis. Recent reports of the anti-inflammatory, antioxidant, antifibrotic, and regenerative properties of mesenchymal stem cells (MSCs) indicate that they may serve as potential novel treatments for kidney disease-particularly DKD. However, current MSC-based therapies for DKD are at the initial clinical stage of research with the precise underlying mechanisms requiring further investigation. Current studies have predominantly concentrated on the renal protective effects mediated by classical signaling pathways such as Wnt/β-catenin, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1)/Smad, and nuclear factor-erythroid 2-related factor 2 (Nrf2), whereas other potentially relevant pathways remain insufficiently investigated. This review comprehensively discusses the key MSC-regulated signaling pathways and their therapeutic potential to provide a theoretical foundation for DKD-related drug development and its clinical translation.