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.