x4 human immunodeficiency virus type 1 gp120 promotes human hepatic stellate cell activation and collagen i expression through interactions with cxcr4x4人类免疫缺陷病毒1型胶原蛋白gp120促进人类肝星状细胞激活和我通过与趋化因子受体cxcr4相互作用表达式.pdfVIP

X4 Human Immunodeficiency Virus Type 1 gp120 Promotes Human Hepatic Stellate Cell Activation and Collagen I Expression through Interactions with CXCR4 1,2 1 2 1 1 Feng Hong , Yedidya Saiman , Chuanping Si , Arevik Mosoian , Meena B. Bansal * 1 Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Department of Immunology, Jining Medical College, Jining, China Abstract Background Aims: Patients coinfected with HIV-1 and HCV develop more rapid liver fibrosis than patients monoinfected with HCV. HIV RNA levels correlate with fibrosis progression implicating HIV directly in the fibrotic process. While activated hepatic stellate cells (HSCs) express the 2 major HIV chemokine coreceptors, CXCR4 and CCR5, little is known about the pro- fibrogenic effects of the HIV-1 envelope protein, gp120, on HSCs. We therefore examined the in vitro impact of X4 gp120 on HSC activation, collagen I expression, and underlying signaling pathways and examined the in vivo expression of gp120 in HIV/HCV coinfected livers. Methods: Primary human HSCs and LX-2 cells, a human HSC line, were challenged with X4 gp120 and expression of fibrogenic markers assessed by qRT-PCR and Western blot +/ 2 either CXCR4-targeted shRNA or anti-CXCR4 neutralizing antibody. Downstream intracellular signaling pathways were evaluated with Western blot and pre-treatment with specific pathway inhibitors. Gp120 immunostaining was performed on HIV/HCV coinfected liver biopsies. Results: X4 gp 120 significantly increased expression of alpha-smooth muscle actin (a-SMA) and collagen I in HSCs which was blocked by pre-incubation with either CXCR4-targeted shRNA or anti-CXCR4 neutralizing antibody. Furthermore, X4 gp120 promoted