HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis

Background & Aims: Activated hepatic stellate cells (HSCs) located in the Disse's space play a crucial role in liver fibrosis. HAb18G/CD147, a tumor-related glycoprotein, is highly expressed in hepatocellular carcinoma cells and fibroblasts. Whether HAb18G/CD147 plays an important role in the hepatic fibrogenesis is unknown. Methods: Immunohistochemistry for HAb18G/CD147 and alpha-smooth muscle actin expression in diseased liver tissues was used for correlation analysis. The function of HAb18G/CD147 in fibrogenesis was evaluated with the human HSCs LX-2 cell line and carbon tetrachloride-induced mouse liver fibrosis model. The specific antibody HAb 1 8 targeting HAb18G/CD147 was injected intravenously into the mouse to investigate whether HAbl8G/CD147 could be a potential target for liver fibrosis treatment. Results: HAb18G/CD147 is highly expressed on activated HSCs in the sinusoid. The positive rates of HAb18G/CD147 expression in human HBV-related liver cirrhosis, liver biopsy with HBV and liver adjacent to hemangioma were 95.6% (65/68), 14.8% (8/54) and 6.4% (8/125), respectively. HAbl8G/CD147 expression was significantly correlated with the Child-Pugh grade (r = 0.2848, p = 0.0186) and with the expression of.-smooth muscle actin in HSCs (r = 0.4434, p = 0.0002) in liver cirrhosis. Transforming growth factor-beta 1 upregulated HAb18G/CD147 expression in growth factor-beta 1 upregulated HAb18G/CD147 expression in growth factor-beta 1 upregulated HAb18G/CD147 expression in LX-2 cells. Transfection of HAb18G/CD147 promoted the profibrogenic genes expression. In mouse liver fibrosis model, HAb 18G/CD1 47 expression increased with the development of fibrogenesis and decreased during the liver fibrosis spontaneous recovery. The HAb18 targeting HAb18G/CD-147 could attenuate liver fibrosis. Conclusions: These data suggest that HAb18G/CD147 plays a role in HSC activation and is a potential therapeutic target in fibrosis/cirrhosis. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.