title: Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yunwu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Mengke
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Dean
authors.initials: D
authors.lastname: Tian
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D006367:HeLa Cells; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System / Q000502:physiology; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019899:Paracrine Communication / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015850:Interleukin-6; D036961:Matrix Attachment Region Binding Proteins; D010982:Platelet-Derived Growth Factor; C076189:SATB1 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C075278:platelet-derived growth factor A; D055513:Connective Tissue Growth Factor