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S100A4 promotes liver fibrosis via activation of hepatic stellate cells, Journal of Hepatology,Available online 9 August 2014

发布时间:2014年09月05日

Journal of Hepatology,Available online 9 August 2014,DOI: 10.1016/j.jhep.2014.07.035Get rights and content

S100A4 promotes liver fibrosis via activation of hepatic stellate cells

Lin Chena, b, c, 1, Jie Lia, b, c, 1, Jinhua Zhanga, b, Chengliang Daia, b, c, Xiaoman Liua, b, Jun Wangd, Zhitao Gaoe, Hongyan Guof, Rui Wangf, Shichun Luf, Fusheng Wangg, Henghui Zhangh, Hongsong Chenh, Xiaolong Fani, Shengdian Wangj, Zhihai Qina

Abstract

Background & Aims
S100A4 has been linked to fibrosis of several organs as a marker for fibroblasts. However, the role of S100A4 itself in fibrosis development has little been investigated. Herein, we determined whether S100A4 regulates liver fibrogenesis and examined its mechanism by focusing on 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 human HSC line LX-2 cells. Levels of serum S100A4 in cirrhotic patients were determined by ELISA.

Results

S100A4 was found to be secreted by a subpopulation of macrophages and promote liver fibrosis development. It accumulated in the liver during progression of liver fibrosis and activated HSCs in mice. In vitro studies demonstrated that S100A4 induced overexpression of alpha-smooth muscle actin through c-myb in HSCs. Both selective depletion of S100A4-expressing cells and knockdown of S100A4 in liver by RNA interference resulted in a reduction of liver fibrosis following injury. Importantly, increased S100A4 levels in both liver tissue and serum correlated positively with liver fibrosis in human.

Conclusions

S100A4 promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrosis therapies.

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文章链接:http://www.sciencedirect.com/science/article/pii/S0168827814005418

 

 

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