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We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) receptor EP4. Paricalcitol was injected into IR\u2010exposed HK\u20102 cells and mice subjected to bilateral kidney ischemia for 23\u2009min and reperfusion for 24\u2009hr. Paricalcitol prevented IR\u2010induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B) in IR\u2010exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals. In vivo studies showed that paricalcitol improved renal dysfunction and tubular necrosis after IR injury and cotreatment with EP4 antagonist inhibited the protective effects of paricalcitol. Phosphorylation of Akt was increased and nuclear translocation of p65 NF\u2010<jats:italic>\u03ba<\/jats:italic>B was decreased in paricalcitol\u2010treated mice with IR injury, which was reversed by EP4 blockade. Paricalcitol decreased oxidative stress and apoptosis in renal IR injury. Paricalcitol also attenuated the infiltration of inflammatory cells and production of proinflammatory cytokines after IR injury. EP4 antagonist abolished these antioxidant, anti\u2010inflammatory, and antiapoptotic effects. The EP4 plays a pivotal role in the protective effects of paricalcitol in renal IR injury.<\/jats:p>","DOI":"10.1155\/2017\/5031926","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T21:01:43Z","timestamp":1490821303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Paricalcitol Pretreatment Attenuates Renal Ischemia\u2010Reperfusion Injury via Prostaglandin E<sub>2<\/sub> Receptor EP4 Pathway"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-4955","authenticated-orcid":false,"given":"Yu Ah","family":"Hong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keum Jin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So 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