Repression of liver cirrhosis achieved by inhibitory effect of miR-454 on hepatic stellate cells activation and proliferation via Wnt10a

被引:11
|
作者
Wang, Yong-Zhen [1 ]
Zhang, Wei [2 ]
Wang, Yan-Hua [3 ]
Fu, Xi-Lin [4 ]
Xue, Chen-Qi [1 ]
机构
[1] Nanjing Univ Chinese Med, Nanjing Hosp 2, Dept Intervent Radiol & Vasc Surg, 1 Zhongfu Rd, Nanjing 210003, Jiangsu, Peoples R China
[2] Henan Inst Sci & Technol, Coll Anim Sci & Vet Med, Xinxiang 453003, Henan, Peoples R China
[3] Nanjing Univ Chinese Med, Nanjing Hosp 2, Dept Ultrasound, Nanjing 210003, Jiangsu, Peoples R China
[4] Nanjing Univ Chinese Med, Nanjing Hosp 2, Dept Hepatopathy, Nanjing 210003, Jiangsu, Peoples R China
来源
JOURNAL OF BIOCHEMISTRY | 2019年 / 165卷 / 04期
关键词
hepatic stellate cell; liver cirrhosis; miR-454; TGF-1; Wnt10a; WNT/BETA-CATENIN PATHWAY; FIBROSIS; QUIESCENT;
D O I
10.1093/jb/mvy111
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
As is known, hepatic stellate cells (HSCs) activation contributes to liver cirrhosis. This study aims to find out the acting mechanisms of miR-454 inhibiting the activation and proliferation of hepatic stellate cells. The expression of Col1A1, -smooth muscle actin (-SMA) and Wnt10a were determined by western blot, and the miR-454 level was determined by quantitative real-time PCR in this study. We took two objects as experiment subjects, one was liver cirrhosis rats, and the other was transforming growth factor (TGF)-1-stimulated HSC-T6 cells. After activated with TGF-1 and transfected with microRNA-454 mimic, separately or successively, the changes on the Col1A1 and -SMA expression, HSC proliferation, miR-454 level and Wnt10a expression were examined in HSC-T6 cells, respectively. Interaction between miR-454 and Wnt10a was evaluated with dual luciferase reporter assay. MiR-454 expression was down-regulated in tissues of liver cirrhosis rats. TGF-1 caused the down-regulation of the miR-454 in HSC-T6 cells. MiR-454 inhibited the activation and proliferation of HSC-T6 cells. Wnt10a had a targeting relationship with miR-454. TGF-1 promoted HSC-T6 activation and proliferation via down-regulating miR-454 expression, which further up-regulated Wnt10a expression. MiR-454 mimic inhibited cirrhosis progression in liver cirrhosis rats. MiR-454 can inhibit the activation and proliferation of HSCs via suppressing the expression of Wnt10a, to restrain liver cirrhosis.
引用
收藏
页码:361 / 367
页数:7
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