Abstract
Objective: To observe the effect of miR-217 on angiotensin II (AngII)-induced hepatic stellate cells (HSCs) activation, and carbon tetrachloride (CCl4)-induced overexpression in mice, so as to clarify miR-217 role in liver fibrosis. Methods: HSCs were stimulated with AngⅡ and the changes condition in the expression level of miR-217 were detected. HSCs were divided into control group, AngII-treated group and AngⅡ+miR-217-treated group. The expression levels of alpha-smooth muscle actin, fibroblast-specific protein 1 and collagen Ⅰ (Collagen Ⅰ) in each group were detected. The target gene of mir-217 was screened and verified by Targetscan and Dual luciferase gene reporter assay. Real-time quantitative PCR and Western blot were used to detect the effect of miR-217 on the expression level of transforming growth factor beta type Ⅱ receptor (TGFBR2). A CCl4-induced mouse liver fibrosis model was constructed. Masson staining and Sirius red staining were used to detect the effect of miR-217 overexpression on the progression of liver fibrosis in CCl4 mice. Data of two groups were compared using t-test. Data of multiple groups were statistically analyzed with one-way ANOVA. Results: The expression level of miR-217 was downregulated by AngⅡ-stimulated HSC cells. The expression levels of α-smooth muscle actin, fibroblast-specific protein 1 and Collagen Ⅰ induced by AngⅡ was inhibited by miR-217 mimics transfection. The 3'-UTR of TGFBR2 had specifically bind miR-217. The mRNA and protein expression levels of TGFBR2 was inhibited with miR-217 mimics transfection in HSCs. The overexpression of miR-217 had inhibited the expression levels of Collagen Ⅰ and Ⅲ in CCl4 mice and alleviated the progression of liver fibrosis . Conclusion: miR-217 regulates liver fibrosis by targeting TGFBR2, inhibits AngII-induced HSC activation, and slows down the process of liver fibrosis in CCl4 mice, suggesting that miR-217 may have an inhibitory effect on liver fibrosis.