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Placenta. 2015 Sep;36(9):1002-10. doi: 10.1016/j.placenta.2015.07.123. Epub 2015 Jul 14.

The role of Delta-like 4 ligand/Notch-ephrin-B2 cascade in the pathogenesis of preeclampsia by regulating functions of endothelial progenitor cell.

Author information

1
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
2
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: medzouli@163.com.

Abstract

INTRODUCTION:

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.

DISCUSSION:

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.

KEYWORDS:

Dll4/Notch; EPCs; Ephrin-B2; Preeclampsia

PMID:
26212082
DOI:
10.1016/j.placenta.2015.07.123
[Indexed for MEDLINE]

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