title: Nerve growth factor regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes via PI3K/mTOR pathway.
abstract: 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.
authors.affiliation: Medical College, Shandong University, Jinan, Shandong, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Qilu Hospital of Shandong University, Jinan, China JinZHANG6@yeah.net.
authors.forename: W Y
authors.initials: WY
authors.lastname: Ma
mesh_terms: D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020928:Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one