title: Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported.
  
  
  METHODS
  To examine the effect of HGF on liver injury in NASH, we generated a murine steatohepatitis model on an HGF overexpression transgenic (Tg) background, and fed the mice a methionine- and choline-deficient diet (MCD).
  
  
  RESULTS
  In mice fed the MCD diet, serum ALT levels and the inflammation score for the Tg mice were significantly lower than those for the wild-type (Wt) control mice (P < 0.01). The index of lipid peroxidation increased in the liver of the Wt mice as demonstrated by thiobarbituric acid-reactive substances. Furthermore, the liver fibrosis in Tg mice was dramatically suppressed in comparison to that in Wt mice. The gene expression of matrix metalloprotease-13 in the Tg mice was significantly increased in comparison to that of the Wt mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay showed the apoptotic cells to significantly decrease in number in the Tg mice in comparison to the Wt mice fed the MCD diet (P < 0.01).
  
  
  CONCLUSIONS
  Hepatocyte growth factor ameliorated liver inflammation and fibrosis in a murine model of NASH as a result of the anti-oxidative and anti-apoptotic effect, and the induction of fibrinolysis.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tojima
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan. kakizaki@showa.gunma-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kakizaki
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kosone
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Horiguchi
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori