| HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis. | |
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MedLine Citation:
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PMID: 22878468 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 α-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 HAb18 targeting HAb18G/CD147 was injected intravenously into the mouse to investigate whether HAb18G/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. HAb18G/CD147 expression was significantly correlated with the Child-Pugh grade (r =0.2848, P =0.0186) and with the expression of α-smooth muscle actin in HSCs (r =0.4434, P =0.0002) in liver cirrhosis. Transforming growth factor-β1 upregulated HAb18G/CD147 expression in LX-2 cells. Transfection of HAb18G/CD147 promoted the profibrogenic genes expression. In mouse liver fibrosis model, HAb18G/CD147 expression increased with the development of fibrogenesis and decreased during the liver fibrosis spontaneous recovery. The HAb18 targeting HAb18G/CD147 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. |
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Authors:
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Da-Wei Zhang; You-Xu Zhao; Ding Wei; Ya-Lin Li; Yang Zhang; Jiao Wu; Jing Xu; Chen Changsheng; Hao Tang; Wei Zhang; Li Gong; Ying Han; Zhi-Nan Chen; Huijie Bian |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-6 |
Journal Detail:
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Title: Journal of hepatology Volume: - ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier B.V. |
Affiliation:
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Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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