Study of the negative regulation of transforming growth factor beta type II receptor to inhibit the occurrence and development of liver fibrosis with miR-217
10.3760/cma.j.cn501113-20200203-00026
- VernacularTitle:miR-217负调控转化生长因子β受体Ⅱ抑制肝纤维化发生及发展的研究
- Author:
Yiwei GUO
1
;
Panjiao PANG
;
Yongkun SUN
Author Information
1. 新乡医学院人体解剖与组织胚胎学系，新乡 453003
- Keywords:
Liver fibrosis;
Hepatic stellate cells;
Angiotensin Ⅱ;
miR-217;
Transforming growth factor beta receptor Ⅱ
- From:
Chinese Journal of Hepatology
2022;30(7):752-757
- CountryChina
- Language:Chinese
-
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.
