Background: Exosomes can be secreted from bone marrow mesenchymal stem
cells (BMSCs) to extracellular space and exert anti-fibrotic effects, but the
underlying mechanisms remain to be elucidated. Methods: 5/6 subtotal
nephrotomy (SNx) rat models and TGF-1-induced human renal proximal tubular
epithelial cells (HRPTEpiCs) were established to simulate renal fibrosis. Renal
function and fibrosis were assessed by Hematoxylin and Eeosin (HE) staining,
Masson staining, immunohistochemistry, and western blot. The expression of Smad
7/Smurf 2 was detected in rats and HRPTEpiCs by western blot, and a further
potential mechanism was explored using si-Smurf 2. Results: BMSC-Exo
improved renal function, reduced the fibrotic region, down-regulated the
expression of fibronectin, Collagen-I, -SMA, and up-regulated
E-cadherin in SNx models. In vitro study demonstrated that knocking down
the expression of Smurf 2 significantly increased the expression of Smad 7, which
could be enhanced by BMSC-Exo. BMSC-Exo could alleviate the fibrosis induced by
TGF-1 in tubular epithelial cells and enhanced the protective effect of
si-Smurf 2 on renal fibrosis. Conclusions: BMSC-Exo inhibited renal
fibrosis both in vivo and in vitro, partially, by regulating
the Smurf 2/Smad 7 axis. BMSC-Exo enhanced the protective effect of si-Smurf 2 on
fibrosis induced by transforming growth factor-1 (TGF-1).