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Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice.
- Source :
-
Journal of hepatology [J Hepatol] 2016 Jan; Vol. 64 (1), pp. 110-7. Date of Electronic Publication: 2015 Aug 31. - Publication Year :
- 2016
-
Abstract
- 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-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.<br />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.<br />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-β/Smad2 signaling pathway, proved by increasing Smad7 expression, resulting in reduced collagen production and α-smooth muscle actin expression in the activated HSCs.<br />Conclusion: Hic-5 deficiency attenuates the activation of HSCs and liver fibrosis though reducing the TGF-β/Smad2 signaling by upregulation of Smad7. Thus, Hic-5 can be regarded as a potential therapeutic target for liver fibrosis.<br /> (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Actins analysis
Animals
Carbon Tetrachloride
Cells, Cultured
Cytoskeletal Proteins analysis
DNA-Binding Proteins analysis
Humans
LIM Domain Proteins analysis
Mice
Mice, Inbred C57BL
Smad2 Protein metabolism
Transforming Growth Factor beta physiology
Up-Regulation
Cytoskeletal Proteins deficiency
DNA-Binding Proteins deficiency
Hepatic Stellate Cells physiology
LIM Domain Proteins deficiency
Liver Cirrhosis etiology
Smad7 Protein physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 64
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 26334580
- Full Text :
- https://doi.org/10.1016/j.jhep.2015.08.026