|S100A4 promotes liver fibrosis via activation of hepatic stellate cells|
|Chen, Lin1,2,3; Li, Jie1,2,3; Zhang, Jinhua1,2; Dai, Chengliang1,2,3; Liu, Xiaoman1,2; Wang, Jun4; Gao, Zhitao5; Guo, Hongyan6; Wang, Rui6; Lu, Shichun6; Wang, Fusheng7; Zhang, Henghui8; Chen, Hongsong8; Fan, Xiaolong9; Wang, Shengdian10; Qin, Zhihai1,2|
|关键词||S100A4 Liver fibrosis Hepatic stellate cells Activation|
|刊名||JOURNAL OF HEPATOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Gastroenterology & Hepatology|
|研究领域[WOS]||Gastroenterology & Hepatology|
|关键词[WOS]||METASTASIS-ASSOCIATED PROTEIN ; FIBROBLAST-SPECIFIC PROTEIN-1 ; TISSUE FIBROSIS ; MOUSE-LIVER ; MECHANISMS ; EXPRESSION ; ROLES ; TRANSLATION ; MACROPHAGES ; REGRESSION|
Background & Aims: S100A4 has been linked to the fibrosis of several organs due to its role as a fibroblast-specific marker. However, the role of S100A4 itself in the development of fibrosis has not been much investigated. Here, we determined whether S100A4 regulates liver fibrogenesis and examined its mechanism by focusing on the activation of hepatic stellate cells (HSCs).
Methods: S100A4 deficient mice were used to determine the role of S100A4 in liver fibrogenesis. The effect of S100A4 on HSC activation was estimated by using primary mouse HSCs and the human HSC cell line LX-2. Serum levels of S100A4 in cirrhotic patients were determined by ELISA.
Results: S100A4 was found to be secreted by a subpopulation of macrophages and to promote the development of liver fibrosis. It accumulated in the liver during the progression of liver fibrosis and activated HSCs in mice. In vitro studies demonstrated that S100A4 induced the overexpression of alpha-smooth muscle actin through c-Myb in HSCs. Both, the selective depletion of S100A4-expressing cells and knockdown of S100A4 in the liver by RNA interference, resulted in a reduction of liver fibrosis following injury. Importantly, increased S100A4 levels in both the liver tissue and serum correlated positively with liver fibrosis in humans.
Conclusions: S100A4 promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrotic therapies. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
|项目编号||2012CB917103 ; 2012CB934003 ; 91229203 ; 81030049 ; 81370543|
|资助机构||Ministry of Science and Technology of China ; National Natural Science Foundation of China, China|
|作者单位||1.Xinxiang Med Univ, Xinxiang, Peoples R China|
2.Beijing 302 Hosp, Dept Infect Dis, Beijing, Peoples R China
3.Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA
4.Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China
5.Chinese Acad Sci, Inst Biophys, Chinese Acad Sci Univ Tokyo Joint Lab Struct Viro, Beijing 100101, Peoples R China
6.Univ Chinese Acad Sci, Beijing, Peoples R China
7.Capital Med Univ, Beijing YouAn Hosp, Beijing, Peoples R China
8.Peking Univ, Inst Hepatol, Peoples Hosp, Beijing 100871, Peoples R China
9.Beijing Normal Univ, Lab Neurosci & Brain Dev, Beijing Key Lab Gene Resource & Mol Dev, Beijing 100875, Peoples R China
10.Chinese Acad Sci, Inst Biophys, Ctr Infect & Immun, Key Lab Infect & Immun, Beijing 100101, Peoples R China
|Chen, Lin,Li, Jie,Zhang, Jinhua,et al. S100A4 promotes liver fibrosis via activation of hepatic stellate cells[J]. JOURNAL OF HEPATOLOGY,2015,62(1):156-164.|
|APA||Chen, Lin.,Li, Jie.,Zhang, Jinhua.,Dai, Chengliang.,Liu, Xiaoman.,...&Qin, Zhihai.(2015).S100A4 promotes liver fibrosis via activation of hepatic stellate cells.JOURNAL OF HEPATOLOGY,62(1),156-164.|
|MLA||Chen, Lin,et al."S100A4 promotes liver fibrosis via activation of hepatic stellate cells".JOURNAL OF HEPATOLOGY 62.1(2015):156-164.|