Document Detail

HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis.
MedLine Citation:
PMID:  22878468     Owner:  NLM     Status:  MEDLINE    
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.
Da-Wei Zhang; You-Xu Zhao; Ding Wei; Ya-Lin Li; Yang Zhang; Jiao Wu; Jing Xu; Changsheng Chen; Hao Tang; Wei Zhang; Li Gong; Ying Han; Zhi-Nan Chen; Huijie Bian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-07
Journal Detail:
Title:  Journal of hepatology     Volume:  57     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-06-21     Revised Date:  2013-07-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1283-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
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MeSH Terms
Antigens, CD147 / physiology*
Carbon Tetrachloride / metabolism,  toxicity
Cell Line
Hepatic Stellate Cells / physiology*
Liver Cirrhosis / etiology,  therapy*
Mice, Inbred BALB C
Transforming Growth Factor beta1 / physiology
Reg. No./Substance:
0/BSG protein, human; 0/Transforming Growth Factor beta1; 136894-56-9/Antigens, CD147; 56-23-5/Carbon Tetrachloride
Comment In:
J Hepatol. 2013 Apr;58(4):836-7   [PMID:  23195621 ]
J Hepatol. 2013 Apr;58(4):837-8   [PMID:  23195620 ]

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