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

Background and Aim. Aberrant activationof theTGF-𝛽1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs.Theaim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic ratmodel 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-SMAin 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 diethylnitrosamineinduced liver fibrotic rats (𝑃 < 0.05). 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 (𝑃 < 0.05).ThemiR-195 mimics activated HSCs, further elevated miR-195 and 𝛼-SMA (𝑃 < 0.01), and reduced the Smad7 level (𝑃 < 0.05). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and 𝛼-SMA (𝑃 < 0.01), and upregulated the expression of Smad7 (𝑃 < 0.05). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7. [ABSTRACT FROM AUTHOR]