Protease-activated receptor 2 (PAR2) mediates vascular smooth muscle cell migration induced by tissue factor/factor VIIa complex.
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.


CONCLUSIONS
These results suggest that PAR2 in SMCs plays a crucial role in the cell migration induced by TF/FVIIa complex.
Marutsuka
Kousuke
K
First Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. kmaru@post.miyazaki-med.ac.jp
Hatakeyama
Kinta
K
Sato
Yuichiro
Y
Yamashita
Atsushi
A
Sumiyoshi
Akinobu
A
Asada
Yujiro
Y
D002465:Cell Movement / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism / Q000502:physiology*; D014357:Trypsin
D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; D013925:Thromboplastin; D015942:Factor VIIa; D014357:Trypsin