title: Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo.
abstract: BACKGROUND
  Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown.
  
  
  METHODS
  For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-a and TGF-beta1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry.
  
  
  RESULTS
  In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-a and in LX-2 cells by TGF-beta1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model.
  
  
  CONCLUSIONS
  Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Jian
authors.affiliation: Department of Gerontology, Shanghai Putuo Central Hospital, Shanghai Traditional Chinese Medicine University, Shanghai 200062, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Hu
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Hu
authors.affiliation: Department of Gerontology, Shanghai Putuo Central Hospital, Shanghai Traditional Chinese Medicine University, Shanghai 200062, China.
authors.forename: Gen-Mei
authors.initials: GM
authors.lastname: Yang
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Zheng
authors.affiliation: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D017931:DNA Primers; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; C492066:CCN4 protein, rat; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride