title: HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.
abstract: Accelerated fibrosis in patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been a major cause of mortality in the highly active anti-retroviral therapy (HAART) era. However, the role of co-infection in accelerating the progression of liver fibrosis, particularly with regard to the effects of co-infection on hepatic stellate cells (HSCs), remains unclear. We hypothesized that HIV and HCV induce liver fibrosis synergistically by altering the regulation of epimorphin production, and thereby indirectly alter HSC function. Here, we examined the effects of epimorphin on HSC proliferation and invasion, and the changes in fibrogenesis-related gene activity in HSCs (LX2) in the presence of inactivated CXCR4-tropic HIV and HCV (JFH1). The combination of HIV and HCV significantly increased epimorphin expression, which increased the proliferation and invasion capabilities of HSCs. Epimorphin also induced the expression of profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP1) in an extracellular signal-regulated kinase (ERK)-dependent manner. These data indicated that the effects of HIV/HCV co-infection on hepatic fibrosis might be mediated in part by EPM. Strategies to limit the expression of EPM might represent a novel therapeutic approach to prevent the progression of hepatic fibrosis during HIV/HCV co-infection.
authors.affiliation: Medical School of Chinese PLA, Beijing, China.|Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Enqiang
authors.initials: E
authors.lastname: Qin
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Nie
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Tumor Radiotherapy Center, Beijing 302 Hospital, Beijing, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Lv
authors.affiliation: Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Medical School of Chinese PLA, Beijing, China.|Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Medical School of Chinese PLA, Beijing, China.|Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Wang
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D060085:Coinfection / Q000235:genetics / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D020935:MAP Kinase Signaling System / Q000502:physiology; D050827:Syntaxin 1 / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C074558:STX2 protein, human; D050827:Syntaxin 1