Abstract:Objective: The present study aims to investigate the role of protease-activated receptor 2 (PAR2) in the regulation of human endothelial progenitor cells (EPCs) function. Methods: EPCs were stimulated with tryptase (a natural agonist of PAR2), SLIGKV-NH2 (a synthetic agonist of PAR2) and FSLLRY-NH2 (an antagonist of PAR2). Cell proliferation and migration were evaluated by EdU incorporation and Transwell model. Expression of the cytokines and receptors were estimated by qPCR and ELISA. Level of intercellular RhoA was assessed by western blot analysis. And RhoA antagonist Y-27632 was also applied to determine whether the effects of PAR2 activation can be abolished by RhoA inhibition. Results: The agonists of PAR2 dramatically inhibited EPCs proliferation and migration in a dose-dependent manner (P<0.05). PAR2 activation markedly suppressed the expression of VEGF-A, VEGFR-2, SDF-1 and CXCR4 (P<0.05). All these effects can be abolished by the PAR2 antagonist (P<0.05). And PAR2 activation increased the level of RhoA in EPCs, which was also repressed by FS (P<0.05). Y-27632 notably reversed the influence of PAR2 activation on EPCs proliferation and migration (P<0.05). Conclusion: Activation of PAR2 blunted EPCs proliferation and migration via RhoA signal, hinting a potential role of PAR2 as a novel target for the modulation of endothelial regeneration and vasculogenesis.