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Sci."],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Preeclampsia (PE) is a hypertensive pregnancy disorder marked by impaired trophoblast invasion and placental vascular dysfunction, resulting in severe maternal and fetal complications. Placental growth factor (PlGF) is critical for proper placental angiogenesis and is transcriptionally regulated by glial cell missing-1 (GCM1), a downstream effector of peroxisome proliferator-activated receptor-gamma (PPAR\u03b3). Decreased PPAR\u03b3 activity in PE may therefore contribute to diminished PlGF levels, worsening placental pathology. In this study, we investigated the mechanistic role of rosiglitazone, a PPAR\u03b3 agonist, in rescuing PlGF expression under 1.5% oxygen\/reoxygenation stress mimicking PE. Using JEG-3 trophoblast cells, we show that rosiglitazone enhances PPAR\u03b3 nuclear translocation, leading to increased GCM1 and cyto-protective heme oxygenase-1 (HO-1) expression, and subsequent upregulation of PlGF production under both 21% oxygen and 1.5% oxygen\/reoxygenation conditions. Pharmacologic inhibition of PPAR\u03b3 with T0070907 or siRNA-mediated knockdown abrogated these effects, underscoring PPAR\u03b3\u2019s essential role in maintaining GCM1-driven PlGF expression. Notably, rosiglitazone treatment rescued PlGF production in 1.5% oxygen\/reoxygenation-stressed cells, highlighting a potential therapeutic strategy to mitigate placental dysfunction. These findings define the PPAR\u03b3-GCM1-PlGF axis as a mechanistic cornerstone of placental health and suggest that pharmacological activation of PPAR\u03b3 may offer clinical benefit in improving pregnancy outcomes in PE.<\/jats:p>","DOI":"10.1007\/s43032-025-01868-w","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T15:38:19Z","timestamp":1745854699000},"page":"1864-1875","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rosiglitazone-Mediated Activation of PPAR\u03b3 Induces PlGF Expression in Trophoblast Cells"],"prefix":"10.1007","volume":"32","author":[{"given":"Pinki","family":"Nandi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chidambra","family":"Halari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mavis","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elakkiya","family":"Prabaharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahil","family":"Sarajideen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-445X","authenticated-orcid":false,"given":"Sascha","family":"Drewlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"issue":"7","key":"1868_CR1","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","volume":"124","author":"S Rana","year":"2019","unstructured":"Rana S, Lemoine E, Granger JP, Karumanchi SA, Preeclampsia. 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