title: EPHB4, a down stream target of IFN-γ/STAT1 signal pathway, regulates endothelial activation possibly contributing to the development of preeclampsia.
abstract: Preeclampsia is characterized by endothelial activation and excessive inflammation, of which interferon (IFN)-γ is a potent inducer. Eph receptor B4 (EPHB4) also involved in endothelial activation in inflammation. Their role and relationship in preeclampsia remain unclear.
  
  
  
  Intercellular adhesion molecular (ICAM)-1 was employed as the hallmark of endothelial activation. The serum levels of IFN-γ and the expression of EPHB4 and ICAM-1 were assessed by ELISA, qRT-PCR and WB, respectively. Primary human umbilical vein endothelial cells (HUVECs) were treated with IFN-γ of different concentration or for different times to determine the effect of IFN-γ on EPHB4 and ICAM-1 expression. Overexpression and shRNA constructs, chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to clarify the regulation mechanism of IFN-γ/STAT1 on EPHB4 resulting in HUVECs activation. Endothelial-trophoblast co-culture model was used to illustrate the role of EPHB4 in the process of activated endothelial cells resisting trophoblast invasion.
  
  
  
  IFN-γ, EPHB4 and ICAM-1 expression were elevated in preeclampsia. IFN-γ induced HUVECs activation through EPHB4 expression. ChIP and luciferase assays revealed that IFN-γ promoted EPHB4 transcription by STAT-1 binding to EPHB4 promoter. EPHB4 probably involved in resisting trophoblasts displacement by IFN-γ-activated HUVECs.
  
  
  
  This study uncovered the character of EPHB4-regulating endothelial activation in the pathogenesis of preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Minglian
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SunshineLeo@hust.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D036224:Receptor, EphB4 / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D036224:Receptor, EphB4
keywords: EPHB4; IFN-γ/STAT1; endothelial activation; endothelial-trophoblasts coculture; preeclampsia