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

被引：53
作者：
Zhanet, Da-Wei [1 ,2 ]
Zhao, You-Xu [1 ,2 ]
Wei, Ding [1 ,2 ]
Li, Ya-Lin [3 ]
Zhang, Yang [1 ,2 ]
Wu, Jiao [1 ,2 ]
Xu, Jing [1 ,2 ]
Chen, Changsheng [4 ]
Tang, Hao [1 ,2 ]
Zhang, Wei [5 ]
Gong, Li [5 ]
Han, Ying [6 ]
Chen, Zhi-Nan [1 ,2 ]
Bian, Huijie [1 ,2 ]
机构：
[1] Fourth Mil Med Univ, Cell Engn Res Ctr, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Dept Cell Biol, Xian 710032, Peoples R China
[3] Weinan Normal Univ, Coll Chem & Life Sci, Weinan, Peoples R China
[4] Fourth Mil Med Univ, Dept Hlth Stat, Xian 710032, Peoples R China
[5] Fourth Mil Med Univ, Tangdu Hosp, Dept Pathol, Xian 710032, Peoples R China
[6] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian 710032, Peoples R China
来源：
JOURNAL OF HEPATOLOGY | 2012年 / 57卷 / 06期
基金：
中国国家自然科学基金;
关键词：
EMMPRIN; TGF-beta; 1; Antibody; Liver cirrhosis; Myofibroblasts; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA; ALPHA-SMA; EXPRESSION; TRANSPLANTATION; PATHOGENESIS; HEPATOCYTES; REGRESSION; METUXIMAB; CIRRHOSIS;
D O I：
10.1016/j.jhep.2012.07.042
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
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.
引用
收藏
页码：1283 / 1291
页数：9
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