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

Thymosin β4 has multi-functional roles in cell physiology, but little is known about its mechanism(s) of action. We previously reported that thymosin β4 stimulated angiogenesis through the induction of vascular endothelial growth factor (VEGF). To identify the mechanism of VEGF induction by thymosin β4, we have used a luciferase assay system with VEGF in the 5' promoter region. We also analyzed the effect of thymosin β4 on VEGF mRNA stability and on the expression and stability of hypoxia-inducible factor (HIF)-1α. We found that thymosin β4 induces VEGF expression by an increase in the stability of HIF-1α protein. Analysis of the expression patterns of thymosin β4 and HIF-1α in colon cancer tissue microarray showed that thymosin β4 and HIF-1α co-localized in these biopsies. These data show that thymosin β4 induces the expression of VEGF indirectly by increasing the protein stability of HIF-1α.

Research Highlight
► We first identify that thymosin beta-4 up-regulates VEGF expression indirectly by increasing the stability of HIF-1alpha protein which is the key protein induce the expression of VEGF. These findings also suggest regulation mechanism of VEGF expression and angiogenesis in nomoxic condition and thymosin beta-4 is the regulatory protein control the VEGF expression in normoxic condition.