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

• Published in: Journal of neuroimmunology 2005-06, Vol.163 (1), p.84-91
• Main Authors: Jeong, Hyun-Ja, Kim, Joon-Bae, Hong, Seung-Heon, An, Nyeon-Hyoung, Kim, Min-Sun, Park, Byung-Rim, Park, Rae-Kil, Kim, Hyung-Min
• Format: Article
• Language: English
• Subjects: Animals; Cell Hypoxia - physiology; Cell Line; Cells, Cultured; DNA-Binding Proteins - physiology; Ear, Inner - metabolism; Enzyme Activation - physiology; Hair cells; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-inducible factor-1α; Mice; Mice, Transgenic; Mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - physiology; Nuclear Proteins - physiology; Stress, Physiological - metabolism; Stress, Physiological - physiopathology; Transcription Factors - physiology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2005.02.019

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The iron-chelator desferrioxamine (DFX) increased the expression of hypoxia-inducible factor (HIF)-1α 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-1α stabilization in vivo. These results indicate that VEGF production is regulated via MAPK and HIF-1α under hypoxic condition in the inner ear.