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    
Abstract/OtherAbstract:
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.
Authors:
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.
Affiliation:
Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD147 / physiology*
Apoptosis
Carbon Tetrachloride / metabolism,  toxicity
Cell Line
Hepatic Stellate Cells / physiology*
Humans
Liver Cirrhosis / etiology,  therapy*
Mice
Mice, Inbred BALB C
Transforming Growth Factor beta1 / physiology
Chemical
Reg. No./Substance:
0/BSG protein, human; 0/Transforming Growth Factor beta1; 136894-56-9/Antigens, CD147; 56-23-5/Carbon Tetrachloride
Comments/Corrections
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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