Vascular endothelial growth factor is regulated by hypoxic stress via MAPK and HIF-1 alpha in the inner ear

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The iron-chelator desferrioxamine (DFX) increased the expression of hypoxia-inducible factor (HIF)-1alpha in the hair cell line, HEI-OC1. The increased VEGF production by DFX was inhibited by iron. DFX also induced the activation of mitogen-activated protein kinase (MAPK) on HEI-OC1. The increased VEGF production by DFX was inhibited by a specific inhibitor of MAPK. In addition, DFX induced the VEGF production and HIF-1alpha stabilization in vivo. These results indicate that VEGF production is regulated via MAPK and HIF-1alpha under hypoxic condition in the inner ear.