Thymosin ß4 reduces senescence of endothelial progenitor cells via the PI3K/Akt/eNOS signal transduction pathway.

Molecular medicine reports

PubMedID: 23151623

Li J, Yu L, Zhao Y, Fu G, Zhou B. Thymosin ß4 reduces senescence of endothelial progenitor cells via the PI3K/Akt/eNOS signal transduction pathway. Mol Med Rep. 2013;7(2):598-602.
We previously demonstrated that thymosin ß4 (Tß4) regulates a variety of endothelial progenitor cell (EPC) functions, including cell migration, proliferation, survival and angiogenesis. However, the effect of Tß4 on the senescence of circulating EPCs remains unclear. In the present study, the effect of Tß4 on EPC senescence and the signal transduction pathways involved in this process was investigated. Circulating EPCs isolated from healthy volunteers were cultured in the absence or presence of Tß4 and various signal cascade inhibitors. Tß4 inhibited EPC senescence in a concentration-dependent manner. In addition, Tß4 increased telomerase activity and expression of telomerase reverse transcriptase mRNA in EPCs. Tß4 also regulated the expression of p21, p27 and cyclin D1. The effects of Tß4 on EPC senescence were eliminated by the phosphoinositide 3'-kinase (PI3K) inhibitor, wortmannin and the endothelial nitric oxide synthase inhibitor, L-nitroarginine methyl ester hydrochloride (L-NAME). In conclusion, the inhibitory effect on EPC senescence mediated by Tß4 may be attributed, at least in part, to activation of the PI3K-Akt-eNOS signaling pathway.