Up-regulation of plasminogen activator inhibitor-1 (PAI-1) by thymosinb 4 in endothelial cells
Abstract number: P0147
Al-Nedawi* K., Szemraj J., Bednarek* R., Swiatkowska M., Cierniewska-Cieslak A., Dastych J., Wyczolkowska* J., Cierniewski C. S.
Int'l Institute of Molecular and Cell Biology, Poland Medical University of Lodz, Poland; *Polish Academy of Science, Poland;
Thymosin b 4, a 4.9-kDa polypeptide primarily known as a main G-actin sequestering peptide, is present in high concentrations in various cells. It has been identified as an agent mediating endothelial cell migration, angiogenesis and accelerating the process of wound healing. Recent observations indicated that large amounts of thymosin b 4 can be released from the activated platelets suggesting its role in the regulation of clot formation. Due to the fact that PAI-1 is involved in regulation of fibrinolysis, vascularization and cell migration, in the present study we have investigated the effect of thymosin b 4 on the expression of PAI-1 in human endothelial cells. We have found that thymosin b 4 up-regulates the expression of PAI-1 measured both at the level of mRNA and protein synthesis in a concentration-dependent manner. Thymosin b 4 significantly activated PAI-1 promoter in two systems: (a) EA.hy 926 cells transfected with plasmid p800 LUC containing PAI-1 promoter fragment (+71 to -800) (b) in the same cells transiently transfected with PAI-1 promoter linked with GFP. Thymosin b 4 mediated up-regulation of PAI-1 involved activation of MAPK cascade showed that MAPK and JNK activity increased in response to thymosin b 4. JNK phosphorylation was associated with the increased phosphorylation of JNK substrate c-jun. Using specific substrates for u-PA and plasmin we showed that PAI-1 released from EA. hy 926 cells by thymosin b 4 markedly reduced their activity on the surface of the cells. In conclusion, our results suggest that thymosin b 4 may be an important factor that regulates expression of PAI-1 in endothelial cells and modulate the extracellular fibrynolytic activity.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2003; 1 Supplement 1 July: abstract number
|Subject:||Procoagulant and fibrinolytic activity|
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