title: The role of Delta-like 4 ligand/Notch-ephrin-B2 cascade in the pathogenesis of preeclampsia by regulating functions of endothelial progenitor cell.
abstract: BACKGROUND
  Preeclampsia is a hypertensive complication in pregnancy, closely related to endothelial dysfunction. Endothelial progenitor cells (EPCs) have the capacity for endothelial repair. Both Ephrin-B2 and Dll4/Notch pathway play critical roles in various steps of angiogenesis. In addition, there is an up-regulation of ephrin-B2 expression consequent to Dll4/Notch activation in endothelial cells (ECs). However, the roles of ephrin-B2 and Dll4/Notch signaling on EPCs, as well as the relationship between them, have not been completely characterized.
  
  
  METHODS
  We analyzed expression of ephrin-B2 in the EPCs and placenta from preeclampsia and normal pregnancy. Then up-regulation and down-regulation strategies were employed to detect the effects of ephrin-B2 on EPC proliferation, differentiation, migration and HUVEC-tube formation. The effects of Dll4/Notch signaling on EPCs' functions were determined by repeating the assays in the presence of Dll4 or DAPT as agonists or antagonists of Notch signaling, respectively.
  
  
  RESULTS
  Ephrin-B2 expression increased notably in preeclampsia EPCs and placenta, compared with controls. Up-regulation of ephrin-B2 impaired EPCs' proliferation, differentiation, migration and HUVEC-tube formation capabilities. In contrast, down-regulation of ephrin-B2 in EPCs, resulted in the opposite effects. In addition, activation of Dll4/Notch signaling led to increased expression of ephrin-B2 and subsequent inhibition of EPCs activity.
  
  
  CONCLUSIONS
  Ephrin-B2, a downstream of Dll4/Notch signaling pathway, might be act as an inhibitor of EPC-mediated vasculogenesis in vitro, as well as a potential target in the effort to promote angiogenesis of patients with preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: medzouli@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002465:Cell Movement; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D036388:Ephrin-B2 / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000378:metabolism; D011247:Pregnancy; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036388:Ephrin-B2; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch
keywords: Dll4/Notch; EPCs; Ephrin-B2; Preeclampsia