title: Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats.
abstract: BACKGROUND
  Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis. In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma (PPAR-gamma) on rat hepatic fibrosis.
  
  
  METHODS
  Hepatic fibrosis in rats was induced by CCl4 for 2 weeks (early fibrosis) and 8 weeks (sustained fibrosis). The rats were randomly divided into four groups: normal control, fibrosis, blank vector, and PPAR-gamma. They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-gamma gene by portal vein injection. The liver of the rats was examined histologically and hydroxyproline was assessed. In vitro primary hepatic stellate cells (HSCs) were infected with the recombinant lentiviral expression vector carrying the rat PPAR-gamma gene. The status of HSC proliferation was measured by the MTT assay. The protein levels of PPAR-gamma, alpha-smooth muscle actin (alpha-SMA) and type I collagen expression were evaluated by the Western blotting method.
  
  
  RESULTS
  In vitro studies revealed that expression of PPAR-gamma inhibited expression of alpha-SMA and type I collagen in activated HSCs (P<0.01) as well as HSC proliferation (P<0.01). In vivo experiments indicated that in the early hepatic fibrosis group, the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-gamma transfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group; whereas the expressions of PPAR-gamma and alpha-SMA were different compared to the hepatic fibrosis group (P<0.01). In the sustained hepatic fibrosis group, there were significant differences in the hydroxyproline content and the expression of PPAR-gamma, alpha-SMA, and type I collagen between each group.
  
  
  CONCLUSIONS
  PPAR-gamma can inhibit HSC proliferation and hepatic fibrosis, and suppress alpha-SMA and type I collagen expression.
authors.affiliation: Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jia-Peng
authors.initials: JP
authors.lastname: Xu
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Sun
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wu
authors.forename: Meng
authors.initials: M
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D000199:Actins; D002251:Carbon Tetrachloride; D024042:Collagen Type I; D006909:Hydroxyproline; D047495:PPAR gamma; C498862:Acta2 protein, rat