{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:48:50Z","timestamp":1791254930888,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T00:00:00Z","timestamp":1242604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preeclampsia, which affects approximately 5\u20138% of all pregnancies and is one of the leading causes of maternal and fetal morbidity and mortality, is a pregnancy induced complex of multiple pathological changes, including elevated blood pressure, proteinuria and edema manifested after 20 weeks gestation. There is growing evidence that placental stresses during pregnancy, notably hypoxia, and an increase in circulating soluble Flt\u20101 (sFlt\u20101) are important in the etiopathogenesis of preeclampsia. How placental stress results in elevated sFlt\u20101 expression is currently unknown. Here we provide novel data implicating the Gadd45a stress sensor protein as an upstream modulator of pathophysiological changes observed in preeclampsia. It is shown that Gadd45a expression and activation of its downstream effector p38 kinase are elevated in preeclamptic placentas compared to non\u2010preeclamptic controls, and correlate with elevated sFlt\u20101. Furthermore, a regulatory loop is demonstrated where stress, including hypoxia, IL\u20106 or hypertonic stress, caused induction of Gadd45a, leading to p38 activation and ultimately increasing sFlt\u20101 secretion in endothelial cells. These data provide a compelling working frame to further test the role of Gadd45 stress sensors in the etiology of preeclampsia, and set the stage for considering novel therapeutic regimens, including p38 inhibitors, for treatment of preeclampsia. J. Cell. Physiol. 220: 632\u2013639, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21800","type":"journal-article","created":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T17:48:12Z","timestamp":1242668892000},"page":"632-639","source":"Crossref","is-referenced-by-count":36,"title":["Gadd45a stress signaling regulates sFlt\u20101 expression in preeclampsia"],"prefix":"10.1002","volume":"220","author":[{"given":"Yali","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan A.","family":"Liebermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Tront","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer 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