title: HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis.
abstract: OBJECTIVE
  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.affiliation: Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.forename: You-Xu
authors.initials: YX
authors.lastname: Zhao
authors.forename: Ding
authors.initials: D
authors.lastname: Wei
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiao
authors.initials: J
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.forename: Huijie
authors.initials: H
authors.lastname: Bian
mesh_terms: D000818:Animals; D017209:Apoptosis; D051926:Basigin / Q000502:physiology*; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: C497886:BSG protein, human; D053773:Transforming Growth Factor beta1; D051926:Basigin; D002251:Carbon Tetrachloride