{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:18:46Z","timestamp":1791245926320,"version":"4.1.0"},"reference-count":28,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Intervillous blood flow increases after 10 wk of gestation and results in exposure of trophoblast cells to oxygen. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. The oxygen-regulated early events of trophoblast differentiation are mediated by TGF-\u03b23. TGF-\u03b23 plays a vital role in trophoblast differentiation, and its overexpression can be found in preeclamptic placenta. We sought to determine the mechanism of TGF-\u03b23 expression through hypoxia-inducible factor (HIF)-1. We show that HIF-1\u03b1 and TGF-\u03b23 are overexpressed in preeclamptic placenta. Hypoxia not only transactivates the TGF-\u03b23 promoter activity but also enhances endogenous TGF-\u03b23 expression. Using the TGF-\u03b23 promoter deletion mutants, we show that the region between \u221290 and \u221260, which contains a putative HIF-1 consensus motif, is crucial for HIF-1-mediated transactivation. Electrophoretic mobility shift assays show that HIF-1 binds to the oligonucleotide containing the HIF-1 motif. Also, introduction of an antisense oligonucleotide for HIF-1 diminishes TGF-\u03b23 expression during hypoxia, indicating that the up-regulation of TGF-\u03b23 by hypoxia is mediated through HIF-1. Our results provide evidence that regulation of TGF-\u03b23 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia.<\/jats:p>","DOI":"10.1210\/en.2003-1639","type":"journal-article","created":{"date-parts":[[2004,5,25]],"date-time":"2004-05-25T00:43:40Z","timestamp":1085445820000},"page":"4113-4118","source":"Crossref","is-referenced-by-count":85,"title":["Hypoxia-Inducible Factor-1 Transactivates Transforming Growth Factor-\u03b23 in Trophoblast"],"prefix":"10.1210","volume":"145","author":[{"given":"Hirotaka","family":"Nishi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology (H.N., T.N., M.H., Y.O., O.I., K.I.), Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Nakada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (H.N., T.N., M.H., Y.O., O.I., K.I.), Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyasu","family":"Hokamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (H.N., T.N., M.H., Y.O., O.I., K.I.), Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Osakabe","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (H.N., T.N., M.H., Y.O., O.I., K.I.), Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Itokazu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (H.N., T.N., M.H., Y.O., O.I., K.I.), Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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