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

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-beta 1 (TGF-beta 1) and matrix metalloproteinase-13 (MMP-13) were examined by real-time polymerase chain reaction. The protein levels of alpha-smooth muscle actin (alpha-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-beta 1 mRNA and alpha-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.