{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T22:00:45Z","timestamp":1772143245066,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370733"],"award-info":[{"award-number":["81370733"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p>Preeclampsia is characterized by endothelial activation and excessive inflammation, of which interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>)\u2010\u03b3 is a potent inducer. Eph receptor B4 (<jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4) also involved in endothelial activation in inflammation. Their role and relationship in preeclampsia remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>Intercellular adhesion molecular (<jats:styled-content style=\"fixed-case\">ICAM<\/jats:styled-content>)\u20101 was employed as the hallmark of endothelial activation. The serum levels of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 and the expression of <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">ICAM<\/jats:styled-content>\u20101 were assessed by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">WB<\/jats:styled-content>, respectively. Primary human umbilical vein endothelial cells (<jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s) were treated with <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 of different concentration or for different times to determine the effect of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 on <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">ICAM<\/jats:styled-content>\u20101 expression. Overexpression and sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> constructs, chromatin immunoprecipitation (Ch<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>) and luciferase assays were conducted to clarify the regulation mechanism of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>1\u00a0on <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 resulting in <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s activation. Endothelial\u2013trophoblast co\u2010culture model was used to illustrate the role of <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 in the process of activated endothelial cells resisting trophoblast invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3, <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">ICAM<\/jats:styled-content>\u20101 expression were elevated in preeclampsia. <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 induced <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s activation through <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 expression. Ch<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content> and luciferase assays revealed that <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 promoted <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 transcription by <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>\u20101 binding to <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 promoter. <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4 probably involved in resisting trophoblasts displacement by <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3\u2010activated <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study uncovered the character of <jats:styled-content style=\"fixed-case\">EPHB<\/jats:styled-content>4\u2010regulating endothelial activation in the pathogenesis of preeclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12555","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T06:32:48Z","timestamp":1472020368000},"page":"307-317","source":"Crossref","is-referenced-by-count":15,"title":["<scp>EPHB<\/scp>4, a down stream target of <scp>IFN<\/scp>\u2010\u03b3\/<scp>STAT<\/scp>1 signal pathway, regulates endothelial activation possibly contributing to the development of preeclampsia"],"prefix":"10.1111","volume":"76","author":[{"given":"Xiaoping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 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