{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T10:41:20Z","timestamp":1717843280997},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\/Aims: <\/jats:bold> Hepatocyte growth factor (HGF) inhibits liver fibrosis induced by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) in animal models. NK2 is a natural splice variant of HGF, but its <jats:italic>in vivo<\/jats:italic> function remains to be elucidated. We investigated the <jats:italic>in vivo<\/jats:italic> effects of NK2 on CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> NK2 transgenic mice and wild\u2010type (WT) mice were injected intraperitoneally with CCl<jats:sub>4<\/jats:sub> twice a week. The extent of hepatic fibrosis was evaluated by Azan\u2013Mallory staining. Expression levels of mRNAs of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) and matrix metalloproteinase\u201013 (MMP\u201013) were examined by real\u2010time polymerase chain reaction. The protein levels of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), c\u2010Met and its phosphorylation were determined by Western blot analysis.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> Liver fibrosis was significantly more severe in NK2 transgenic mice than in WT mice. CCl<jats:sub>4<\/jats:sub> administration increased the expression levels of TGF\u2010\u03b21 mRNA and \u03b1\u2010SMA protein, and decreased the expression of MMP\u201013 mRNA in livers of NK2 transgenic mice compared with those of WT mice. c\u2010Met protein expression in the liver was compatible with the degree of fibrosis. As for c\u2010Met activation, no difference was found between NK2 and WT livers.<\/jats:p><jats:p><jats:bold>Conclusion: <\/jats:bold> Overexpression of NK2 acts as an antagonist of HGF and promotes liver fibrosis in CCl<jats:sub>4<\/jats:sub>\u2010induced chronic liver injury.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2007.01616.x","type":"journal-article","created":{"date-parts":[[2010,8,27]],"date-time":"2010-08-27T13:25:18Z","timestamp":1282915518000},"page":"126-131","source":"Crossref","is-referenced-by-count":10,"title":["Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride\u2010induced chronic liver injury"],"prefix":"10.1111","volume":"28","author":[{"given":"Satoshi","family":"Hagiwara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kosone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naondo","family":"Sohara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatomo","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,11]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91253-1"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113334"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/327239a0"},{"key":"e_1_2_5_5_2","first-page":"3314","article-title":"Purification 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