{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:53:31Z","timestamp":1790009611212,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T00:00:00Z","timestamp":1344470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> We previously demonstrated that heparin\u2010binding epidermal growth factor\u2010like growth factor (HB\u2010EGF) is induced in response to several liver injuries. Because the HB\u2010EGF knockout (KO) mice die <jats:italic>in utero<\/jats:italic> or immediately after birth due to cardiac defects, the loss of function study <jats:italic>in vivo<\/jats:italic> is limited. Here, we generated liver\u2010specific HB\u2010EGF conditional knockout mice using the interferon\u2010inducible Mx\u20101 promoter driven cre recombinase transgene and investigated its role during acute liver injury.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> We induced acute liver injury by a single i.p. injection of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) in HB\u2010EGF KO mice and wild\u2010type mice and liver damage was assessed by biochemical and immunohistochemical analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular mechanism of HB\u2010EGF\u2010dependent anti\u2010apoptosis and wound\u2010healing process of the liver <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> HB\u2010EGF KO mice exhibited a significant increase of alanine aminotransferase level and also showed a significant increase in the number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining at 24\u2003h after CCl<jats:sub>4<\/jats:sub> injection. We also demonstrated that HB\u2010EGF treatment inhibited tumor necrosis factor\u2010\u03b1\u2010induced apoptosis of AML12 mouse hepatocytes and promoted the wound\u2010healing response of these cells.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> This study showed that HB\u2010EGF plays a protective role during acute liver injury.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2012.01074.x","type":"journal-article","created":{"date-parts":[[2012,7,11]],"date-time":"2012-07-11T08:39:10Z","timestamp":1341995950000},"page":"384-393","source":"Crossref","is-referenced-by-count":23,"title":["Conditional knockout of heparin\u2010binding epidermal growth factor\u2010like growth factor in the liver accelerates carbon tetrachloride\u2010induced liver injury in 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