Open AccessHepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx
Author(s) -
Jin Gong,
Wei Tu,
Jian Han,
Jianzhong He,
Jingmei Liu,
Ping Han,
Yunwu Wang,
Mengke Li,
Mei Liu,
Jiazhi Liao,
Dean Tian
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep37717
Subject(s) - hbx , hepatic stellate cell , ctgf , hepatic fibrosis , cancer research , downregulation and upregulation , hepatitis b virus , fibrosis , paracrine signalling , biology , growth factor , immunology , medicine , endocrinology , virus , biochemistry , receptor , gene
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover, we suggested HBV encoded x protein (HBx) induced SATB1 expression through activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes promoted the activation and proliferation of hepatic stellate cells (HSCs) by secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine activation of stellate cells in HBV-related fibrosis.