Abstract Previous studies have demonstrated that mice disrupted with the cyclooxygenase-2 gene showed much more severe liver damage compared with wild-type mice after liver injury, and prostaglandins (PGs) such as PGE 1/2 and PGI 2 have decreased hepatic injury, but the mechanisms by which prostaglandins exhibit protective action on the liver have yet to be addressed. In the present study, we investigated the mechanism of the protective action of PGI 2 using the synthetic IP receptor agonist ONO-1301. In primary cultures of hepatocytes and nonparenchymal liver cells, ONO-1301 did not show protective action directly on hepatocytes, whereas it stimulated expression of hepatocyte growth factor (HGF) in nonparenchymal liver cells. In mice, peroral administration of ONO-1301 increased hepatic gene expression and protein levels of HGF. Injections of CCl4 induced acute liver injury in mice, but the onset of acute liver injury was strongly suppressed by administration of ONO-1301. The increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by CCl4 were suppressed by 10 mg/kg ONO-1301 to 39.4 and 33.6%, respectively. When neutralizing antibody against HGF was administered with ONO-1301 and CCl4, the decreases by ONO-1301 in serum ALT and AST, apoptotic liver cells, and expansion of necrotic areas in liver tissue were strongly reversed by neutralization of endogenous HGF. These results indicate that ONO-1301 increases expression of HGF and that hepatoprotective action of ONO-1301 in CCl4-induced liver injury may be attributable to its activity to induce expression of HGF, at least in part. The potential for involvement of HGF-Met-mediated signaling in the hepatotrophic action of endogenous prostaglandins generated by injury-dependent cyclooxygenase-2 induction is considerable. cyclooxygenase-2 growth factor Met ONO-1301 prostaglandin Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print December 2011 , doi: 10.​1152/​ajpgi.​00216.​2011 AJP - GI February 2012 vol. 302 no. 4 G420-G429 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpgi.00216.2011v1 302/4/G420 most recent Classifications Liver and Biliary Tract Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Xu, Q. Articles by Matsumoto, K. PubMed PubMed citation Articles by Xu, Q. Articles by Matsumoto, K. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of AJP - GI About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0193-1857 Online ISSN: 1522-1547 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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