Podocyte Proteomics Revealed hUCMSC-Exosomes Ameliorate Diabetic Kidney Disease through Inhibiting Talin‑1 Mediated EMT

Background: Podocytes injury drives proteinuria in diabetic kidney disease (DKD). Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have demonstrated therapeutic potential in kidney diseases. However, the effects of hUCMSCs on podocyte injury and the underlying mechanisms in DKD remain unexplored. Methods: Four-dimensional label-free quantitative proteomics was performed on a global analysis of proteins in sorted podocytes from normal mice (NC group), db/db mice (DM group), and db/db mice treated with hUCMSCs (DMT group). Results: HUCMSC-derived exosomes alleviated renal dysfunction and podocyte epithelial-mesenchymal transition (EMT). A total of 1765 proteins were quantified, with enrichment in pathways related to cytoskeleton organization, phagocytosis, oxidative stress, and apoptosis. Talin-1 was downregulated in diabetic podocytes but upregulated following hUCMSC treatment. Talin-1 silencing exacerbated high glucose-induced EMT. Conclusions: This study highlights the potential of hUCMSC-derived exosomes as a therapeutic strategy for DKD by ameliorating Talin-1-mediated podocyte EMT.