MicroRNA-195 Activates Hepatic Stellate Cells In Vitro by Targeting Smad7

Background and Aim. Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamine-induced liver fibrotic rats (). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3′UTR of Smad7 (). The miR-195 mimics activated HSCs, further elevated miR-195 and α-SMA (), and reduced the Smad7 level (). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and -SMA (), and upregulated the expression of Smad7 (). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7.

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