Nerve growth factor regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes via PI3K/mTOR pathway

作者：Zhang, J.; Ma, W. Y.^*

来源：Genetics and Molecular Research, 2014, 13(4): 9324-9335.

DOI：10.4238/2014.January.24.14

• Nerve growth factor
• Hypoxia-inducible factor-1 alpha
• Psoriasis
• Vascular endothelial growth factor
• Keratinocytes

Decades of research have provided the data to confirm the hypothesis that there is bidirectional communication between the central nervous system and the immune system in psoriasis pathogenesis, but the contribution of the cutaneous neural system remains underexplored. In this study, we evaluated the molecular mechanisms by which nerve growth factor (NGF) regulates hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) production. The mRNA and protein levels of VEGF secretion from HaCaT cells by NGF were increased in a concentration-dependent manner. In addition, the NGFinduced increase in VEGF is accompanied by an increase in HIF-1 alpha, but not HIF-2 alpha or HIF-1 beta. However, this increase is abrogated by pretreatment with a mammalian target of rapamycin (mTOR) inhibitor rapamycin. Pharmacologic inhibitors of the Trk tyrosine kinase, PI-3 kinase, and mTOR pathways prevent NGF-stimulated increases in HIF-1 alpha and VEGF. Mutation of the siRNA-mediated silencing of HIF-1 alpha expression blocks NGF-induced increases in VEGF transcription. Our study indicates that NGF regulates the expression of VEGF through the PI3K/mTOR signaling pathway in human HaCaT keratinocytes.

• 出版日期2014
• 单位山东大学