{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:54:14Z","timestamp":1790762054058,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T00:00:00Z","timestamp":1373328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>The hepatic growth factor hepatopoietin Cn (<jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content>) prevents liver injury induced by carbon tetrachloride in rats. Sphingosine 1\u2010phosphate (<jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content>) is a bioactive sphingolipid produced by sphingosine kinase (<jats:styled-content style=\"fixed-case\">SphK<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">S1PRs<\/jats:styled-content>) are involved in liver fibrogenesis and oxidative injury. This work sought to understand the mechanism by which <jats:styled-content style=\"fixed-case\">SphK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">S1PRs<\/jats:styled-content> are involved in the protective effects of <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> on ethanol\u2010induced liver injury and fibrosis. Transgenic mice with liver\u2010specific overexpression of <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HPPCn<jats:sup>liver<\/jats:sup><\/jats:styled-content><jats:sup>+\/+<\/jats:sup>) were generated. Two ethanol feeding protocols were used to assess the protective effect of <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> on acute and chronic liver injury in mice. Specific inhibitors of <jats:styled-content style=\"fixed-case\">S1PR1<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">S1PR2<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">S1PR3<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">siRNA<\/jats:styled-content> were used to examine the roles of <jats:styled-content style=\"fixed-case\">S1PRs<\/jats:styled-content> in hepatic stellate cell (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>) activation and hepatocyte apoptosis. Increased <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> expression in transgenic mice attenuated fibrosis induced by ethanol and carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CCl<jats:sub>4<\/jats:sub><\/jats:styled-content>). Treatment with recombinant human <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> prevented human hepatocyte apoptosis and <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation. <jats:styled-content style=\"fixed-case\">JTE<\/jats:styled-content>\u2010013 or <jats:styled-content style=\"fixed-case\">S1PR2\u2010siRNA<\/jats:styled-content> attenuated the effect of <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> on <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation induced by tumour necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1). Consistent with the effect of <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010dimethylsphingosine (<jats:styled-content style=\"fixed-case\">DMS<\/jats:styled-content>), suramin or <jats:styled-content style=\"fixed-case\">S1PR3\u2010siRNA<\/jats:styled-content> treatment blocked <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content>\u2010induced Erk1\/2 phosphorylation in human hepatocytes. This study demonstrated that <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> attenuated oxidative injury and fibrosis induced by ethanol feeding and that the <jats:styled-content style=\"fixed-case\">SphK1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">S1PRs<\/jats:styled-content> signalling pathway contributes to the protective effect of <jats:styled-content style=\"fixed-case\">HPPCn<\/jats:styled-content> on hepatocyte apoptosis and <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4194","type":"journal-article","created":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T08:42:38Z","timestamp":1373359358000},"page":"365-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hepatopoietin Cn reduces ethanol\u2010induced hepatoxicity via sphingosine kinase 1 and sphingosine 1\u2010phosphate receptors"],"prefix":"10.1002","volume":"230","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Experimental Hematology Beijing Institute of Radiation Medicine  27 Taiping Road Beijing 100850 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyan","family":"Saiyan","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology Beijing Institute of Radiation Medicine  27 Taiping Road Beijing 100850 PR 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