Open AccessNerve growth factor regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes via PI3K/mTOR pathway
Author(s) -
J Zhang,
Wang A.Y
Publication year - 2014
Publication title -
genetics and molecular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.356
H-Index - 48
ISSN - 1676-5680
DOI - 10.4238/2014.january.24.14
Subject(s) - pi3k/akt/mtor pathway , hacat , nerve growth factor , vascular endothelial growth factor , gene silencing , biology , growth factor , angiogenesis , microbiology and biotechnology , vascular endothelial growth factor a , cancer research , hypoxia inducible factors , signal transduction , endocrinology , medicine , cell culture , receptor , vegf receptors , biochemistry , gene , genetics
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-1α (HIF-1α) 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 NGF- induced increase in VEGF is accompanied by an increase in HIF-1α, but not HIF-2α or HIF-1β. 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-1α and VEGF. Mutation of the siRNA-mediated silencing of HIF-1α 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.