{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:06:00Z","timestamp":1791846360871,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T00:00:00Z","timestamp":1336521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)\u2010W envelope gene Syncytin\u20101. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP\u2010kinase p38\u03b1 regulates PPAR\u03b3\/RXR\u03b1 signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPAR\u03b3\/RXR\u03b1 signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin\u20101, other signaling members and CT cell fusions were regulated with PPAR\u03b3\/RXR\u03b1 activators troglitazone and 9\u2010<jats:italic>cis<\/jats:italic>retinoic acid, via protein kinase A and p38\u03b1 inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPAR\u03b3\/RXR\u03b1\u2010response\u2010elements from upstream regulatory elements and the 5\u2032LTR of HERV\u2010W were confirmed with DNA\u2010protein binding assays using nuclear extracts and recombinant PPAR\u03b3\/RXR\u03b1 proteins. These promoter elements were validated with luciferase assays in the presence of PPAR\u03b3\/RXR\u03b1 modulators. Furthermore, troglitazone or 9\u2010<jats:italic>cis<\/jats:italic>retinoic acid treatment of siRNA\u2010PPAR\u03b3 and siRNA\u2010RXR\u03b1 transfected BeWo cells proved the requirement of these proteins for Syncytin\u20101 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38\u03b1, phospho\u2010p38\u03b1, PPAR\u03b3, ABCG2, INSL4 and Syncytin\u20101. Our study characterized PPAR\u03b3\/RXR\u03b1 signaling in human CT and cell fusions identifying Syncytin\u20101 as a new target gene. Based on these results, a disturbed PPAR\u03b3\/RXR\u03b1 pathway could contribute to pathological human pregnancies. J. Cell. Biochem. 113: 2383\u20132396, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24110","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T15:12:19Z","timestamp":1330960339000},"page":"2383-2396","source":"Crossref","is-referenced-by-count":70,"title":["Regulation of the human endogenous retroviral Syncytin\u20101 and cell\u2013cell fusion by the nuclear hormone receptors PPAR\u03b3\/RXR\u03b1 in placentogenesis"],"prefix":"10.1002","volume":"113","author":[{"given":"Matthias","family":"Ruebner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Langbein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela 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