Astragaloside IV attenuates renal fibrosis through repressing epithelial-to-mesenchymal transition by inhibiting microRNA-192 expression: in vivo and in vitro studies.

The aim of this study was to investigate the effect of Astragaloside IV (AS-IV) on renal fibrosis in vivo and in vitro, and further to explore the underlying mechanism. To investigate the effect of AS-IV treatment on renal fibrosis in vivo, mouse renal fibrosis model was established by performing unilateral ureteral occlusion (UUO). The mice in the intervention group of AS-IV were given AS-IV 20 mg/(kg/d) on the day after surgery for 7 consecutive days. Then renal sections were stained with hematoxylin and eosin (H&E) to evaluate the degree of fibrosis. For in vitro study, human kidney tubular epithelial cells induced by (TGF-β1) were performed to research the protective role of AS-IV in anti-fibrosis. Results form the in vivo study showed that AS-IV treatment in UUO mice significantly reduced parenchymal loss and tubular atrophy, indicating that AS-IV treatment attenuated renal fibrosis caused by UUO. TGF-β1 treatment significantly increased the expression of α-SMA, vimentin, collagen I, miR-192 and decreased E-cadherin expression in HK-2 cells, suggesting that TGF-β1 stimulated renal tubulointerstitial fibrosis. Moreover, in TGF-β1 stimulated HK-2 cells, AS-IV clearly inhibited the expression levels of α-SMA, vimentin, collagen I, and miR-192 in a dose-dependent fashion while increased the expression level of E-cadherin in the same manner, indicating that AS-IV functioned the inhibitory role in renal tubulointerstitial fibrosis. Interestingly, we noted that ZEB2 was a direct target of miR-192. The effects of AS-IV on the expression of α-SMA, vimentin, collagen I and E-cadherin were inhibited by miR-192 mimic and aggravated by miR-192 inhibitor. Taken together, our results provided evidence that AS-IV could effectively protect kidney against epithelial fibrosis, and this renoprotective effect involved miR-192. Therefore, AS-IV might be considered as a potential and promising candidate drug for the treatment of renal epithelial fibrosis.