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Since chronic inflammation is characteristics also for heart failure, the aim of this study was to characterize Reg3<jats:italic>\u03b3<\/jats:italic> expression in cardiac inflammatory conditions. Reg3<jats:italic>\u03b3<\/jats:italic> expression was studied in experimental rat models of myocardial infarction (<jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>) and pressure overload in\u00a0vivo. For cell culture studies neonatal rat cardiac myocytes (<jats:styled-content style=\"fixed-case\">NRCM<\/jats:styled-content>s) were used. In addition, adenovirus\u2010mediated gene transfer of upstream mitogen\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>) kinase 3b and p38<jats:italic>\u03b1 <\/jats:italic><jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> in\u00a0vivo and in\u00a0vitro was performed. Reg3<jats:italic>\u03b3 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> (12.8\u2010fold, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and protein (5.8\u2010fold, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) levels were upregulated during the postinfarction remodeling at day 1 after <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>, and angiotensin II (Ang <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>) markedly increased Reg3<jats:italic>\u03b3 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels from 6\u00a0h to 2\u00a0weeks. Immunohistochemistry revealed that the Ang <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\u2010induced expression of Reg3<jats:italic>\u03b3<\/jats:italic> was localized into the cardiac fibroblasts and myofibroblasts of the proliferating connective tissue in the heart. Stretching and treatments with endothelin\u20101, lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>), and fibroblast growth factor\u20101 increased Reg3<jats:italic>\u03b3 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels in <jats:styled-content style=\"fixed-case\">NRCM<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580, a selective p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> inhibitor, markedly attenuated <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> and mechanical stretch\u2010induced upregulation of Reg3<jats:italic>\u03b3<\/jats:italic> gene expression. Moreover, combined overexpression of <jats:styled-content style=\"fixed-case\">MKK<\/jats:styled-content>3bE and <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> p38<jats:italic>\u03b1<\/jats:italic> increased Reg3<jats:italic>\u03b3<\/jats:italic> gene expression in cultured cardiomyocytes in\u00a0vitro and in the rat heart in\u00a0vivo. Our study shows that cardiac stress activates Reg3<jats:italic>\u03b3<\/jats:italic> expression and p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> is an upstream regulator of Reg3<jats:italic>\u03b3<\/jats:italic> gene expression in heart. Altogether our data suggest Reg3<jats:italic>\u03b3<\/jats:italic> is associated with cardiac inflammatory signaling.<\/jats:p>","DOI":"10.14814\/phy2.12996","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T01:19:11Z","timestamp":1477358351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mitogen\u2010activated protein kinase p38 target regenerating islet\u2010derived 3<i>\u03b3<\/i> expression is upregulated in cardiac inflammatory response in the rat heart"],"prefix":"10.14814","volume":"4","author":[{"given":"Hanna","family":"S\u00e4kkinen","sequence":"first","affiliation":[{"name":"Research Unit of Biomedicine, Pharmacology and Toxicology University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jani","family":"Aro","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Pharmacology and Toxicology University 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