Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner

Thymosin beta 4 has multi-functional roles in cell physiology, but little is known about its mechanism(s) of action. We previously reported that thymosin beta 4 stimulated angiogenesis through the induction of vascular endothelial growth factor (VEGF). To identify the mechanism of VEGF induction by thymosin beta 4, we have used a luciferase assay system with VEGF in the 5' promoter region. We also analyzed the effect of thymosin beta 4 on VEGF mRNA stability and on the expression and stability of hypoxia-inducible factor (HIF)-1 alpha. We found that thymosin beta 4 induces VEGF expression by an increase in the stability of HIF-1 alpha protein. Analysis of the expression patterns of thymosin beta 4 and HIF-1 alpha in colon cancer tissue microarray showed that thymosin beta 4 and HIF-1 alpha co-localized in these biopsies. These data show that thymosin beta 4 induces the expression of VEGF indirectly by increasing the protein stability of HIF-1 alpha. (C) 2010 Elsevier B.V. All rights reserved.