Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride-induced chronic liver injury

Authors

Errata

This article is corrected by:

  1. Errata: CORRIGENDUM Volume 28, Issue 4, 582, Article first published online: 12 March 2008

Correspondence
Toshiyuki Otsuka, MD, PhD, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan
Tel: +81 27 220 8127
Fax: +81 27 220 8136
e-mail: tcht-otsuka@tonehoken.or.jp

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.

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