Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis
Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis
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DOI：
10.1007/s12072-011-9301-z
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发表时间：
2012-06
影响因子：
6.6
通讯作者：
H. Tojima;S. Kakizaki;T. Kosone;N. Horiguchi;Y. Yamazaki;Ken Sato;H. Takagi;M. Mori
中科院分区：
文献类型：
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作者：
H. Tojima;S. Kakizaki;T. Kosone;N. Horiguchi;Y. Yamazaki;Ken Sato;H. Takagi;M. Mori
背景肝细胞生长因子（HGF）是一种与肝再生有关的强有力的生长因子，对上皮细胞和非上皮细胞具有多种作用。虽然已经证明HGF可以减少由药物或化学损伤引起的肝脏炎症或纤维化，但是没有报道其对非酒精性脂肪性肝炎（NASH）中肝损伤的作用的检查。结果在喂食MCD饲料的小鼠中，Tg小鼠的血清ALT水平和炎症评分显著低于野生型（Wt）对照小鼠（P<0. 01）。硫代巴比妥酸反应性物质表明，Wt小鼠肝脏中的脂质过氧化反应指数增加。此外，与Wt小鼠相比，Tg小鼠中的肝纤维化被显著抑制。与Wt小鼠相比，Tg小鼠中基质金属蛋白酶-13的基因表达显著增加。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法显示，与喂食MCD饲料的Wt小鼠相比，Tg小鼠中凋亡细胞的数量显著减少（P< 0.01）。结论肝细胞生长因子通过抗氧化、抗凋亡和诱导纤溶作用改善NASH小鼠模型的肝脏炎症和纤维化。
BackgroundHepatocyte 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.MethodsTo 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).ResultsIn 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).ConclusionHepatocyte 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.