Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice

Journal of Hepatology
Xiao-Feng LeiAkira Miyazaki

Abstract

Hydrogen peroxide-inducible clone-5 (Hic-5), also named as transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was found to be induced by TGF-β. Previous studies have shown that TGF-β is a principal mediator of hepatic stellate cell (HSC) activation in liver fibrosis. However, this process remains elusive. In this study, we aimed to define the role of Hic-5 in HSC activation and liver fibrosis. We examined the expression levels of Hic-5 during HSCs activation and in fibrotic liver tissues by quantitative real-time reverse transcriptase polymerase chain reaction, Western blot and immunohistochemistry. Hic-5 knockout (KO) and wild-type (WT) mice were subjected to bile duct ligation (BDL) or carbon tetrachloride (CCl4) injection to induce liver fibrosis. Hic-5 expression was strongly upregulated in activated HSCs of the human fibrotic liver tissue and BDL or CCl4-induced mouse liver fibrosis. Hic-5 deficiency significantly attenuated mouse liver fibrosis and HSC activation. Furthermore, Hic-5 knockdown by siRNA in vivo repressed CCl4-induced liver fibrosis in mice. Mechanistically, the absence of Hic-5 significantly inhibited the TGF-β/Smad2 signaling pathway, proved by increasing Smad7 expression, resulting ...Continue Reading

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Citations

Jan 22, 2017·The Journal of Investigative Dermatology·Zhi-Cheng HuBing Tang
Sep 25, 2018·Cell Death Discovery·Jun YuHuilong Chen
Nov 14, 2019·Cells·Bedair DewidarAnd Nadja Meindl-Beinker
Jan 14, 2017·World Journal of Gastroenterology : WJG·Chong-Yang ZhangChun-Xu Wang
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Cong WangXuebo Pan
Feb 29, 2020·Ci Ji Yi Xue Za Zhi = Tzu-chi Medical Journal·Wen-Sheng Wu
Jan 7, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anjian XuJian Huang
Aug 19, 2017·Experimental Eye Research·Rintaro TsukaharaShigeo Tamiya
Feb 23, 2021·Molecular Therapy. Nucleic Acids·Fang-Tian BuJun Li
Apr 10, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lu YangJiang Deng
Aug 28, 2021·Biomedicines·Yufei YanChangyong Li

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