Open AccessDown‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization
Author(s) -
Wang Hao,
Wang Pan,
Liang Xiaoling,
Li Wenjing,
Yang Mo,
Ma Jihong,
Yue Wei,
Fan Shangrong
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15011
Subject(s) - trophoblast , endothelial protein c receptor , preeclampsia , placentation , microbiology and biotechnology , biology , receptor , spiral artery , placenta , thrombin , cancer research , immunology , biochemistry , fetus , pregnancy , genetics , platelet
Preeclampsia is a severe pregnancy‐related disease that is found in 3%–5% of pregnancies worldwide and is primarily related to the decreased proliferation and invasion of trophoblast cells and abnormal uterine spiral artery remodelling. However, studies on the pathogenesis of placental trophoblasts are insufficient, and the aetiology of PE remains unclear. Here, we report that endothelial protein C receptor (EPCR), a transmembrane glycoprotein, was down‐regulated in placentas from preeclamptic patients. Moreover, lack of EPCR significantly reduced the trophoblast cell proliferation, invasion and tube formation capabilities. Microscale thermophoresis analysis showed that EPCR directly bound to protease‐activated receptor 1 (PAR‐1), a G protein‐coupled receptor. This change resulted in a substantial reduction in active Rac1 and caused excessive actin rearrangement. Our findings reveal a previously unidentified role of EPCR in the regulation of trophoblast proliferation, invasion and tube formation through promotion of actin polymerization, which is required for normal placental development.