Suppressive effect of SATB1 on hepatic stellate cell activation and liver fibrosis in rats

Jiayi He; Jin Gong; Qiang Ding; Qinghai Tan; Ping Han; Jingmei Liu; Zhenzhen Zhou; Wei Tu; Yujia Xia; Wei Yan; Dean Tian

doi:10.1016/j.febslet.2015.04.010

Suppressive effect of SATB1 on hepatic stellate cell activation and liver fibrosis in rats

FEBS Lett. 2015 May 22;589(12):1359-68. doi: 10.1016/j.febslet.2015.04.010. Epub 2015 Apr 17.

Authors

Jiayi He¹, Jin Gong¹, Qiang Ding¹, Qinghai Tan¹, Ping Han¹, Jingmei Liu¹, Zhenzhen Zhou¹, Wei Tu¹, Yujia Xia¹, Wei Yan², Dean Tian³

Affiliations

¹ Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yanwei@tjh.tjmu.edu.cn.
³ Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: datian@tjh.tjmu.edu.cn.

PMID: 25896016
DOI: 10.1016/j.febslet.2015.04.010

Abstract

Liver fibrosis is a worldwide clinical issue. Activation of hepatic stellate cells (HSCs) is the central event during liver fibrosis. We investigated the role of SATB1 in HSC activation and liver fibrogenesis. The results show that SATB1 expression is reduced during HSC activation. Additionally, SATB1 inhibits HSC activation, proliferation, migration, and collagen synthesis. Furthermore, CTGF, a pro-fibrotic agent, is also significantly inhibited by SATB1 through the Ras/Raf-1/MEK/ERK/Ets-1 pathway. In vivo, SATB1 deactivates HSCs and attenuates fibrosis in TAA-induced fibrotic rat livers. These data indicate that SATB1 plays an important role in HSC activation and liver fibrosis.

Keywords: Hepatic stellate cell; Liver fibrosis; Ras/Raf-1/MEK/ERK/Ets-1; SATB1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Animals
Cell Line
Cell Movement
Cell Proliferation
Cells, Cultured
Collagen / biosynthesis
Connective Tissue Growth Factor / antagonists & inhibitors
Connective Tissue Growth Factor / genetics
Connective Tissue Growth Factor / metabolism
Disease Models, Animal*
Gene Expression Regulation*
Gene Silencing
Hepatic Stellate Cells / metabolism*
Hepatic Stellate Cells / pathology
Homeodomain Proteins / antagonists & inhibitors
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Liver Cirrhosis / metabolism*
Liver Cirrhosis / pathology
MAP Kinase Signaling System
Male
Matrix Attachment Region Binding Proteins / antagonists & inhibitors
Matrix Attachment Region Binding Proteins / genetics
Matrix Attachment Region Binding Proteins / metabolism*
Random Allocation
Rats, Sprague-Dawley
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism

Substances

Actins
CCN2 protein, rat
Homeodomain Proteins
Matrix Attachment Region Binding Proteins
Recombinant Proteins
SATB1 protein, human
SATB1 protein, rat
smooth muscle actin, rat
Connective Tissue Growth Factor
Collagen