Brg1 promotes liver fibrosis via activation of hepatic stellate cells

被引：41

作者：

Li, Haijie ^{[1
]}

Lan, Jingqin ^{[1
]}

Han, Caishun ^{[1
]}

Guo, Kaixuan ^{[1
]}

Wang, Guihua ^{[1
]}

Hu, Junbo ^{[1
]}

Gong, Jianping ^{[1
]}

Luo, Xuelai ^{[1
]}

Cao, Zhixin ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Canc Res Inst, Wuhan, Hubei, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2018年 / 364卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Liver fibrosis; Brg1; Hepatic stellate cells; TGF beta/Smad; HEPATOCELLULAR-CARCINOMA; MECHANISMS; EXPRESSION; DIFFERENTIATION; FIBROGENESIS; BLOCKADE; INSIGHTS; CANCER;

D O I：

10.1016/j.yexcr.2018.02.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by the persistent deposition of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Brg1, the core subunit of the SWI/SNF chromatin remodeling complex, has been proved to associated with nonalcoholic steatohepatitis which may progress to cirrhosis. Herein, we determined whether Brg1 regulates liver fibrosis and examined its mechanism by focusing on HSCs activation. In this study, we demonstrate that Brg1 is elevated in human and mouse fibrotic liver tissues and Brg1 mediate the profibrotic response in activated HSCs. Our data indicate that Brg1 regulates the activation of HSCs through TGF beta/Smad signal pathway. Moreover, Brg1 deficiency mice displayed decreased HSCs activation in vitro and liver fibrogenesis after chronic damage by CCl4 administration. In addition, Brg1 expression is positively correlated with liver fibrosis in cirrhotic patients and may be a prognostic factor in HCC. Collectively, we demonstrate that Brg1 promotes liver fibrosis by activating HSCs and may represent a potential target for anti-fibrotic therapies.

引用

页码：191 / 197

页数：7

共 38 条

[1]

Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma [J].