Thymosin β4 Induces Endothelial Progenitor Cell Migration via PI3K/Akt/eNOS Signal Transduction Pathway

Abstract

Thymosin β4, a G-actin-sequestering peptide, has been shown to play an important role in cell migration. However, little is known about the effect of thymosin β4 on circulating endothelial progenitor cell (EPC) directional migration, which is essential for EPC-mediated reendothelialization and neovascularization. In our study, using a transwell migration assay, we showed that thymosin β4 induced EPC migration in a concentration-dependent manner. Western blot analysis revealed that treatment of EPCs with thymosin β4 resulted in a time and concentration-dependent phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinase (ERK)1/2. Functional analysis showed that thymosin β4-induced EPC migration was blocked by phosphatidylinositol 3-kinase inhibitors (LY294002 or wortmannin) or eNOS inhibitor (Nω-nitro-L-arginine methyl ester) but was not significantly attenuated by mitogen-activated protein kinase (MAPK)/ERK inhibitor (PD98059). These findings suggest that thymosin β4 stimulates EPC directional migration via phosphatidylinositol 3-kinase/Akt/eNOS, rather than via MAPK/ERK signal transduction pathway.