The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 2003 Mar;9(3):331-7
Date
02/13/2003Pubmed ID
12579195DOI
10.1038/nm825Scopus ID
2-s2.0-0037349926 (requires institutional sign-in at Scopus site) 230 CitationsAbstract
Disruption of the mouse gene encoding the blood coagulation inhibitor thrombomodulin (Thbd) leads to embryonic lethality caused by an unknown defect in the placenta. We show that the abortion of thrombomodulin-deficient embryos is caused by tissue factor-initiated activation of the blood coagulation cascade at the feto-maternal interface. Activated coagulation factors induce cell death and growth inhibition of placental trophoblast cells by two distinct mechanisms. The death of giant trophoblast cells is caused by conversion of the thrombin substrate fibrinogen to fibrin and subsequent formation of fibrin degradation products. In contrast, the growth arrest of trophoblast cells is not mediated by fibrin, but is a likely result of engagement of protease-activated receptors (PAR)-2 and PAR-4 by coagulation factors. These findings show a new function for the thrombomodulin-protein C system in controlling the growth and survival of trophoblast cells in the placenta. This function is essential for the maintenance of pregnancy.
Author List
Isermann B, Sood R, Pawlinski R, Zogg M, Kalloway S, Degen JL, Mackman N, Weiler HAuthors
Rashmi Sood PhD Associate Professor in the Pathology department at Medical College of WisconsinHartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Abortion, SpontaneousAnimals
Blood Coagulation
Cell Division
Embryo Loss
Embryo, Mammalian
Female
Fibrin
Fibrinogen
Fibrinolysin
In Situ Hybridization
In Situ Nick-End Labeling
Male
Mice
Mice, Inbred C57BL
Placenta
Pregnancy
Pregnancy Maintenance
Protein C
Receptor, PAR-2
Receptors, Thrombin
Thrombin
Thrombomodulin
Thromboplastin
Trophoblasts
