title: Thymosin β4 reduces senescence of endothelial progenitor cells via the PI3K/Akt/eNOS signal transduction pathway.
abstract: We previously demonstrated that thymosin β4 (Tβ4) regulates a variety of endothelial progenitor cell (EPC) functions, including cell migration, proliferation, survival and angiogenesis. However, the effect of Tβ4 on the senescence of circulating EPCs remains unclear. In the present study, the effect of Tβ4 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 Tβ4 and various signal cascade inhibitors. Tβ4 inhibited EPC senescence in a concentration‑dependent manner. In addition, Tβ4 increased telomerase activity and expression of telomerase reverse transcriptase mRNA in EPCs. Tβ4 also regulated the expression of p21, p27 and cyclin D1. The effects of Tβ4 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 Tβ4 may be attributed, at least in part, to activation of the PI3K‑Akt‑eNOS signaling pathway.
authors.affiliation: Department of Cardiology, Biomedical Research (Therapy) Center,                     Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou                     310016, Zhejiang, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guosheng
authors.initials: G
authors.lastname: Fu
authors.forename: Binquan
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D013947:Thymosin / Q000494:pharmacology*; D000077191:Wortmannin; D000099201:Thymosin beta(4)
chemical_list: D000730:Androstadienes; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D019098:Telomerase; D013947:Thymosin; D000077191:Wortmannin; D000099201:Thymosin beta(4)