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Protease-activated receptor 2 (PAR2) mediates vascular smooth muscle cell migration induced by tissue factor/factor
Kousuke Marutsuka1, Kinta Hatakeyama, Yuichiro Sato
1First Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. kmaru@post.miyazaki-med.ac.jp
Unlabelled:
Protease-activated receptor 2 (PAR2) is one of G-protein-coupled receptors able to be activated by trypsin and coagulation factor VIIa. We previously reported that tissue factor/factor VIIa (TF/FVIIa) complex was a strong chemotactic factor for cultured vascular smooth muscle cells (SMCs). The migratory response was dependent on a catalytic activity of FVIIa, and did not involve factor Xa and thrombin generation. In this study, we examined TF/FVIIa-induced SMC migration.
Methods:
The contribution of PAR2 to TF/FVIIa-induced vascular SMC migration was investigated using a modified Boyden's chamber method, and the distribution of PARs in the human coronary arteries and cultured SMCs was also examined.
Results:
Trypsin and PAR2-activating peptide (AP; SLIGKV) stimulated SMC migration in a dose-dependent manner, of which abilities were comparable to those of TF/FVIIa complex and platelet-derived growth factor-BB, but PAR1-AP (TFLLR or SFLLR) or PAR4-AP (AYPGOV) did not elicit the migration. The antisera against PAR2-AP significantly inhibited TF/FVIIa-induced SMC migration, but that of PAR1-AP did not. In immunostaining, both intimal SMCs of the human coronary arteries and cultured SMCs showed positive reaction for PAR2-AP.
Conclusion:
These results suggest that PAR2 in SMCs plays a crucial role in the cell migration induced by TF/FVIIa complex.