胸腺素β4通过PI3K/AKT/eNOS信号转导通路改善内皮祖细胞衰老

We previously showed that thymosin beta4 (Tβ4) regulates a variety of endothelial progenitor cell (EPC) functions, such as cell migration, proliferation, survival, and angiogenesis. However, the effect of Tβ4 on the senescence of circulating EPCs remains unclear. In this study, we investigated the effect of Tβ4 on EPC senescence and the signal transduction pathways involved in this process. Circulating EPCs isolated from healthy volunteers were cultured in the absence or presence of Tβ4 and various signal cascade inhibitors. Tβ4 inhibited EPC senescence in a concentration-dependent manner. Moreover, Tβ4 increased both telomerase activity and expression of telomerase reverse transcriptase (TERT) mRNA in EPCs. Tβ4 also regulated the expression of p21, p27, and cyclin D1. The effects of Tβ4 on EPC senescence were abolished by the PI3K inhibitor wortmannin and by the eNOS inhibitor L-NAME. In conclusion, the inhibitory effect on EPC senescence mediated by Tβ4 could be attributed, at least in part, to activation of the PI3K-Akt-eNOS signaling pathway.