Figure 8.

Proposed mechanism by which exosomes derived from GDNF-modified human adipose mesenchymal stem cells (GDNF-AMSC-exos) ameliorate damage to unilateral ureteral obstruction (UUO)-treated kidneys by activating the SIRT1/eNOS signaling pathway. In UUO-treated kidneys, the number and the size of peritubular capillaries (PTCs) were reduced and endothelial dysfunction occurred. Myofibroblasts and extracellular matrix deposition increased, and kidney hypoxia and renal fibrosis progressed. GDNF was transfected into human adipose mesenchymal stem cells (GDNF-AMSCs) via a lentiviral transfection system, and exosomes were obtained from the supernatants of GDNF-AMSCs through ultracentrifugation. GDNF-AMSC-exos were transplanted into UUO kidneys via tail vein injection and activated an angiogenesis program in surviving PTCs. GDNF-AMSC-exos enhanced sirtuin-1 (SIRT1) signaling, accompanied by increased phosphorylation of the endothelial nitric oxide synthase (p-eNOS) protein. GDNF-AMSC-exos prevented the reduction in the number of PTCs, maintained renal blood flow, and effectively suppressed the induction of myofibroblast progression. Thus, transplantation of GDNF-AMSC-exos can ameliorate kidney hypoxia and inhibit the progression of renal fibrosis.