The endothelial cell protein C receptor (EPCR) is a type 1 transmembrane protein found primarily on endothelium that binds both protein C and activated protein C with similar affinity. EPCR augments the activation of protein C by the thrombin-thrombomodulin complex. To determine the physiological importance of EPCR, we generated EPCR-deficient mice by homologous targeting in embryonic stem cells. Genotyping of progeny obtained from EPCR(+/-) interbreeding indicated that EPCR(-/-) embryos died on or before embryonic day 10.5 (E10.5). Reverse transcriptase-PCR confirmed the absence of EPCR mRNA in EPCR(-/-) embryos. EPCR(-/-) embryos removed from extra-embryonic membranes and tissues at day E7.5 and cultured in vitro developed beyond E10.5, suggesting a role for EPCR in the normal function of the placenta and/or at the materno-embryonic interface. Immunohistochemistry revealed the lack of EPCR in trophoblast giant cells of EPCR(-/-) embryos. These cells, which normally express EPCR, are in direct contact with the maternal circulation and its clotting factors. In EPCR(-/-) embryos, greatly increased fibrin deposition was detected around these cells. To prevent this fibrin deposition, EPCR(+/-)-crossed female mice received a daily subcutaneous injection of enoxaparin through pregnancy. Although some EPCR(-/-) embryos were rescued from midgestational lethality, this regimen yielded no EPCR(-/-) pups. We conclude that EPCR is essential for normal embryonic development. Moreover, EPCR plays a key role in preventing thrombosis at the maternal-embryonic interface.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M207538200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction.
FASEB J
December 2022
Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, Victoria, Australia.
Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize endothelial protein C receptor (EPCR) in preterm preeclampsia, term preeclampsia, and fetal growth restriction (defined by delivery of a small for gestational age [SGA] infant [<10% birthweight centile]) and examine its regulation in primary syncytiotrophoblast. Placental EPCR mRNA and protein were significantly increased in patients with preterm preeclampsia (<34 weeks gestation) compared to gestation-matched controls (p < .
View Article and Find Full Text PDFEmbryonic vascular establishment requires protein C receptor-expressing endothelial progenitors.
Development
June 2022
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Vascular establishment is one of the early events in embryogenesis. It is believed that vessel-initiating endothelial progenitors cluster to form the first primitive vessel. Understanding the molecular identity of these progenitors is crucial in order to elucidate lineage hierarchy.
View Article and Find Full Text PDFCol6a1/CD201 mesenchymal cells regulate intestinal morphogenesis and homeostasis.
Cell Mol Life Sci
December 2021
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (B.S.R.C.) "Alexander Fleming", 16672, Vari, Greece.
Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1 mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1 mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRα telocytes.
View Article and Find Full Text PDFCo-culture of mesenchymal stem cell spheres with hematopoietic stem cells under hypoxia: a cost-effective method to maintain self-renewal and homing marker expression.
Mol Biol Rep
February 2022
Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Background: Hematopoietic stem cell (HSC) transplantation is considered a possible treatment option capable of curing various diseases. The aim of this study was the co-culturing of mesenchymal stem cell (MSC) spheres with HSCs under hypoxic condition to enhance the proliferation, self-renewal, stemness, and homing capacities of HSCs.
Methods And Results: HSCs were expanded after being subjected to different conditions including cytokines without feeder (Cyto), co-culturing with adherent MSCs (MSC), co-culturing with adherent MSCs + hypoxia (MSC + Hyp), co-culturing with MSCs spheres (Sph-MSC), co-culturing with MSCs spheres + hypoxia (Sph-MSC + Hyp), co-culturing with MSC spheres + cytokines (Sph-MSC + Cyto).
Improved efficiencies in the generation of multigene-modified pigs by recloning and using sows as the recipient.
Zygote
February 2022
Department of Microbiology and Immunology; Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
This study was performed to improve production efficiency at the level of recipient pig and donor nuclei of transgenic cloned pigs used for xenotransplantation. To generate transgenic pigs, human endothelial protein C receptor (hEPCR) and human thrombomodulin (hTM) genes were introduced using the F2A expression vector into GalT-/-/hCD55+ porcine neonatal ear fibroblasts used as donor cells and cloned embryos were transferred to the sows and gilts. Cloned fetal kidney cells were also used as donor cells for recloning to increase production efficiency.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!