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- Title
Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride-induced chronic liver injury.
- Authors
Hagiwara, Satoshi; Otsuka, Toshiyuki; Yamazaki, Yuichi; Kosone, Takashi; Sohara, Naondo; Ichikawa, Takeshi; Sato, Ken; Kakizaki, Satoru; Takagi, Hitoshi; Mori, Masatomo
- Abstract
Background/Aims: Hepatocyte growth factor (HGF) inhibits liver fibrosis induced by carbon tetrachloride (CCl4) in animal models. NK2 is a natural splice variant of HGF, but its in vivo function remains to be elucidated. We investigated the in vivo effects of NK2 on CCl4-induced liver fibrosis. Methods: NK2 transgenic mice and wild-type (WT) mice were injected intraperitoneally with CCl4 twice a week. The extent of hepatic fibrosis was evaluated by Azan–Mallory staining. Expression levels of mRNAs of transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-13 (MMP-13) were examined by real-time polymerase chain reaction. The protein levels of α-smooth muscle actin (α-SMA), c-Met and its phosphorylation were determined by Western blot analysis. Results: Liver fibrosis was significantly more severe in NK2 transgenic mice than in WT mice. CCl4 administration increased the expression levels of TGF-β1 mRNA and α-SMA protein, and decreased the expression of MMP-13 mRNA in livers of NK2 transgenic mice compared with those of WT mice. c-Met protein expression in the liver was compatible with the degree of fibrosis. As for c-Met activation, no difference was found between NK2 and WT livers. Conclusion: Overexpression of NK2 acts as an antagonist of HGF and promotes liver fibrosis in CCl4-induced chronic liver injury.
- Subjects
LIVER cells; GROWTH factors; LIVER diseases; ANIMAL models in research; TRANSGENIC mice
- Publication
Liver International, 2008, Vol 28, Issue 1, p126
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/j.1478-3231.2007.01616.x