Role of p38 Mitogen-Activated Protein Kinase in Thrombus Formation
- 1 January 2004
- journal article
- Published by Taylor & Francis in Journal of Receptors and Signal Transduction
- Vol. 24 (4) , 283-296
- https://doi.org/10.1081/rrs-200040324
Abstract
The present study was designed to elucidate the role of p38 mitogen-activated protein kinase (p38) in thrombus formation. We used p38alpha heterozygous (p38alpha+/-) mice and used ferric chloride (FeCl3)-induced carotid artery injury as a model of thrombus formation. The time to thrombotic occlusion induced by FeCl3 in p38alpha+/- mice was prolonged compared to that in wild-type (WT) mice. Platelets prepared from p38alpha+/- mice showed impairment of the aggregatory response to a low concentration of U46619, a thromboxane A2 analogue. Furthermore, platelets prepared from p38alpha+/- mice and activated by U46619 were poorly bound to fibrinogen compared with those from WT mice. Both the expression and activity of tissue factor induced by FeCl3 in WT mice were higher than those in p38alpha+/- mice. These results suggest that p38 plays an important role in thrombus formation by regulating platelet function and tissue factor activity.Keywords
This publication has 31 references indexed in Scilit:
- Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A2 Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding TimeThe Journal of Pharmacology and Experimental Therapeutics, 2004
- Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activityBlood, 2004
- Reduction in Arthritis Severity and Modulation of Immune Function in Tissue Factor Cytoplasmic Domain Mutant MiceThe American Journal of Pathology, 2004
- Thrombin Protease-activated Receptor-1 Signals through Gq- and G13-initiated MAPK Cascades Regulating c-Jun Expression to Induce Cell TransformationJournal of Biological Chemistry, 2003
- Disruption of a single copy of the p38α MAP kinase gene leads to cardioprotection against ischemia–reperfusionBiochemical and Biophysical Research Communications, 2003
- Coordinated Signaling through Both G12/13 and Gi Pathways Is Sufficient to Activate GPIIb/IIIa in Human PlateletsPublished by Elsevier ,2002
- Factor VIIa Induces Tissue Factor-dependent Up-regulation of Interleukin-8 in a Human Keratinocyte LineJournal of Biological Chemistry, 2002
- Essential Role of p38α MAP Kinase in Placental but Not Embryonic Cardiovascular DevelopmentMolecular Cell, 2000
- Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.Journal of Clinical Investigation, 1997
- Thrombin functions as an inflammatory mediator through activation of its receptor.The Journal of Experimental Medicine, 1996