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Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride‐induced chronic liver injury
Author(s) -
Hagiwara Satoshi,
Otsuka Toshiyuki,
Yamazaki Yuichi,
Kosone Takashi,
Sohara Naondo,
Ichikawa Takeshi,
Sato Ken,
Kakizaki Satoru,
Takagi Hitoshi,
Mori Masatomo
Publication year - 2008
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2007.01616.x
Subject(s) - carbon tetrachloride , liver injury , liver fibrosis , fibrosis , medicine , ccl4 , carbon tetrachloride poisoning , gastroenterology , pathology , chemistry , organic chemistry
Background/Aims: Hepatocyte growth factor (HGF) inhibits liver fibrosis induced by carbon tetrachloride (CCl 4 ) 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 CCl 4 ‐induced liver fibrosis. Methods: NK2 transgenic mice and wild‐type (WT) mice were injected intraperitoneally with CCl 4 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. CCl 4 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 CCl 4 ‐induced chronic liver injury.