Thymosin beta4 induces endothelial progenitor cell migration via PI3K/Akt/eNOS signal transduction pathway.
Thymosin beta4, 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 beta4 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 beta4 induced EPC migration in a concentration-dependent manner. Western blot analysis revealed that treatment of EPCs with thymosin beta4 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 beta4-induced EPC migration was blocked by phosphatidylinositol 3-kinase inhibitors (LY294002 or wortmannin) or eNOS inhibitor (Nomega-nitro-L-arginine methyl ester) but was not significantly attenuated by mitogen-activated protein kinase (MAPK)/ERK inhibitor (PD98059). These findings suggest that thymosin beta4 stimulates EPC directional migration via phosphatidylinositol 3-kinase/Akt/eNOS, rather than via MAPK/ERK signal transduction pathway.
Qiu
Fu-Yu
FY
Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Song
Xiao-Xiao
XX
Zheng
Hao
H
Zhao
Yan-Bo
YB
Fu
Guo-Sheng
GS
D015153:Blotting, Western; D018929:Cell Culture Techniques; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013947:Thymosin / Q000494:pharmacology*; D000099201:Thymosin beta(4)
D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013947:Thymosin; D000099201:Thymosin beta(4); C496314:NOS3 protein, human