Coagulation factor Xa signaling: the link between coagulation and inflammatory bowel disease?
Inflammatory bowel disease (IBD) is characterized by activation of the coagulation cascade and it has long been suspected that coagulation is an essential component of this still largely idiopathic group of diseases. The realization that coagulation factors are not only passive mediators in the propagation of coagulation, but also actively engage different cell types by activating proteinase-activated receptors (PARs) has provided mechanistic insight into how coagulation cascade propagation might participate in the progression of IBD. The emergence of PAR(2) as a key player in the progression of IBD has focused attention on its agonist, coagulation factor Xa (FXa). Recent findings on FXa and PAR(2) link the coagulation cascade to the progression of IBD. Here, we propose that FXa-induced PAR(2) activation has an important role in orchestrating intestinal inflammatory and fibroproliferative responses, and that PAR(2) might provide a novel therapeutic target for the management of IBD.
Borensztajn
Keren
K
Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, NL- 9713 EZ, Groningen, The Netherlands. K.S.Borensztajn@amc.uva.nl
Peppelenbosch
Maikel P
MP
Spek
C Arnold
CA
D000818:Animals; D001777:Blood Coagulation; D015951:Factor Xa / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000503:physiopathology*; D008954:Models, Biological; D044462:Receptors, Proteinase-Activated / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
D044462:Receptors, Proteinase-Activated; D015951:Factor Xa