title: Hepatitis B virus e antigen induces activation of rat hepatic stellate cells.
abstract: Chronic hepatitis B virus infection is a major cause of hepatic fibrosis, leading to liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus e antigen (HBeAg) is an accessory protein of HBV, not required for viral replication but important for natural infection in vivo. Hepatic stellate cells (HSCs) are the major producers of excessive extracellular matrix during liver fibrogenesis. Therefore, we examined the influence of HBeAg on HSCs. The rat HSC line HSC-T6 was transfected with HBeAg plasmids, and expression of α-smooth muscle actin, collagen I, transforming growth factor-β1 (TGF-β), and tissue inhibitors of metalloproteinase 1 (TIMP-1) was investigated by quantitative real-time PCR. The proliferation of HSCs was determined by MTS analysis. HBeAg transduction induced up-regulation of these fibrogenic genes and proliferation of HSCs. We found that HBeAg induced TGF-β secretion in HSCs, and the activation of HSCs was prevented by a neutralizing anti-TGF-β antibody. Depletion and addition of HBeAg protein in conditioned medium from HSC-T6 cells transduced with HBeAg indicated that HBeAg directly induced the activation and proliferation of rat primary HSCs. Taken together, HBeAg induces the activation and proliferation of HSCs, mainly mediated by TGF-β, and HBeAg protein purified from cell medium can directly activate HSCs.
authors.affiliation: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Zan
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D051381:Rats; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D006513:Hepatitis B e Antigens; D016212:Transforming Growth Factor beta