Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice
Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice
复制标题
DOI：
10.1016/j.jhep.2015.08.026
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Akira Miyazaki
中科院分区：
文献类型：
--
作者：
Xiao-Feng Lei;Wenguang Fu;Joo-ri Kim-Kaneyama;Tomokatsu Omoto;Takuro Miyazaki;Bo Li;Akira Miyazaki
Background & Aim: 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-b. Previous studies have shown that TGF-b 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..Methods: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..Results: 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-b/Smad2 signaling pathway, proved by increasing Smad7 expression, resulting in reduced collagen production and a-smooth muscle actin expression in the activated HSCs..Conclusion: Hic-5 deficiency attenuates the activation of HSCs and liver fibrosis though reducing the TGF-b/Smad2 signaling by upregulation of Smad7. Thus, Hic-5 can be regarded as a potential therapeutic target for liver fibrosis.
