HIV and HCV Cooperatively Promote Hepatic Fibrogenesis via Induction of Reactive Oxygen Species and NF kappa B

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	HIV and HCV Cooperatively Promote Hepatic Fibrogenesis via Induction of Reactive Oxygen Species and NF kappa B
	Lin, Wenyu ; Wu, Guoyang ; Li, Shaoyong ; Weinberg, Ethan M. ; Kumthip, Kattareeya ; Peng, Lee F. ; Mendez-Navarro, Jorge ; Chen, Wen-Chi ; Jilg, Nikolaus ; Zhao, Hong ; Goto, Kaku ; Zhang, Leiliang ; Brockman, Mark A. ; Schuppan, Detlef ; Chung, Raymond T. ; Zhao H(赵鸿)
刊名	http://dx.doi.org/10.1074/jbc.M110.168286
	2011-01-28
关键词	VIRUS CORE PROTEIN INDUCED LIVER FIBROSIS C VIRUS STELLATE CELLS MITOCHONDRIAL INJURY OXIDATIVE STRESS GENE-EXPRESSION RAT-LIVER ACTIVATION REPLICATION
英文摘要	National Institutes of Health-MGH Center For Human Immunology Pilot/Feasibility Study; National Institutes of Health [AI069939, AI082630, AI066313U19]; HIV/HCV coinfection leads to accelerated hepatic fibrosis progression, with higher rates of cirrhosis, liver failure, and liver death than does HCV mono-infection. However, the pro-fibrogenic role of HIV on hepatocytes and hepatic stellate cells (HSC) has not been fully clarified. We hypothesized that HIV, HCV induce liver fibrosis through altered regulation of the production of extracellular matrix and matrix metalloproteinases. We examined the fibrogenesis- and fibrolysis-related gene activity in LX2 HSC and Huh7.5.1 cells in the presence of inactivated CXCR4 and CCR5 HIV, as well as HCV JFH1 virus. The role of reactive oxygen species (ROS) upon fibrosis gene expression was assessed using the ROS inhibitor. Fibrosis-related transcripts including procollagen alpha 1(I) (CoL1A), TIMP1, and MMP3 mRNA were measured by qPCR. TIMP1 and MMP3 protein expression were assessed by ELISA. We found that inactivated CXCR4 HIV and CCR5 HIV increased CoL1A, and TIMP1 expression in both HSC and Huh7.5.1 cells; the addition of JFH1 HCV further increased CoL1A and TIMP1 expression. CXCR4 HIV and CCR5 HIV induced ROS production in HSC and Huh7.5.1 cells which was further enhanced by JFH1 HCV. The ROS inhibitor DPI abrogated HIV -and HCV-induced CoL1A and TIMP1 expression. HIV and HCV-induced CoL1A and TIMP1 expression were also blocked by NF kappa B siRNA. Our data provide further evidence that HIV and HCV independently regulate hepatic fibrosis progression through the generation of ROS; this regulation occurs in an NF kappa B-dependent fashion. Strategies to limit the viral induction of oxidative stress are warranted to inhibit fibrogenesis.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/69901]
专题	物理技术－已发表论文
推荐引用方式 GB/T 7714	Lin, Wenyu,Wu, Guoyang,Li, Shaoyong,et al. HIV and HCV Cooperatively Promote Hepatic Fibrogenesis via Induction of Reactive Oxygen Species and NF kappa B[J]. http://dx.doi.org/10.1074/jbc.M110.168286,2011.
APA	Lin, Wenyu.,Wu, Guoyang.,Li, Shaoyong.,Weinberg, Ethan M..,Kumthip, Kattareeya.,...&赵鸿.(2011).HIV and HCV Cooperatively Promote Hepatic Fibrogenesis via Induction of Reactive Oxygen Species and NF kappa B.http://dx.doi.org/10.1074/jbc.M110.168286.
MLA	Lin, Wenyu,et al."HIV and HCV Cooperatively Promote Hepatic Fibrogenesis via Induction of Reactive Oxygen Species and NF kappa B".http://dx.doi.org/10.1074/jbc.M110.168286 (2011).