{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:04:58Z","timestamp":1770836698095,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE\u00a0patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HTR\u20108\/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR\u20108\/SVneo cells were analyzed via reverse transcription\u2010quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p\u2010PI3K, p\u2010AKT, PI3K, and AKT protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Upregulation of DR3 obviously inhibited HTR\u20108\/SVneo cells viability, migration, and invasion, as well as promoted HTR\u20108\/SVneo cells apoptosis, as opposed to the control\u2010plasmid group. We also found that DR3\u2010plasmid enhanced cleaved\u2010caspase3 expression, reduced p\u2010PI3K\u00a0and p\u2010AKT protein expression, and p\u2010PI3K\/PI3K or p\u2010AKT\/AKT ratio in HTR\u20108\/SVneo cells. Importantly, IGF\u20101, a PI3K\/AKT signaling pathway agonist, partially reversed the effects of DR3\u2010plasmid on the cell viability, migration, invasion, apoptosis, and PI3K\/AKT signal pathway in HTR\u20108\/SVneo cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DR3 was involved in PE\u00a0through regulating placental trophoblast cell physiology via PI3K\/AKT pathway, which might be a promising therapeutic target for\u00a0PE therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.995","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T11:50:45Z","timestamp":1695815445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Death receptor 3 is involved in preeclampsia through regulating placental trophoblast cell physiology by inactivating the PI3K\/AKT 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