Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization. Issue 6 (30th January 2020)

• Record Type: Journal Article
• Authors: Wang, Hao; Wang, Pan; Liang, Xiaoling; Li, Wenjing; Yang, Mo; Ma, Jihong; Yue, Wei; Fan, Shangrong
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 6(2020)
• Page Start: 3370
• Page End: 3383
• Publication Date: 2020-01-30
• Subjects: cell invasion -- cell proliferation -- endothelial protein C receptor -- preeclampsia -- tube formation; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15011
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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.