title: Brain-derived neurotrophic factor induces migration of endothelial cells through a TrkB-ERK-integrin αVβ3-FAK cascade.
abstract: Brain-derived neurotrophic factor (BDNF) promotes the regeneration of periodontal tissue. Since angiogenesis is important for tissue regeneration, investigating effect of BDNF on endothelial cell function may help to reveal its mechanism, whereby, BDNF promotes periodontal tissue regeneration. In this study, we examined the influence of BDNF on migration in human microvascular endothelial cells (HMVECs), focusing on the effects on extracellular signal-regulated kinase (ERK), integrin α(V)β(3), and focal adhesion kinase (FAK). The migration of endothelial cells was assessed with a modified Boyden chamber and a wound healing assay. The expression of integrin α(V)β(3) and the phosphorylation of ERK and FAK were analyzed by immunoblotting and immunofluorescence microscopy. BDNF (25 ng/ml) induced cell migration. PD98059, an ERK inhibitor, K252a, a specific inhibitor for TrkB, a high affinity receptor of BDNF, and an anti-integrin α(V)β(3) antibody suppressed the BDNF-induced migration. BDNF increased the levels of integrin α(V)β(3) and phosphorylated ERK1/2 and FAK. The ERK inhibitor and TrkB inhibitor also reduced levels of integrin α(V)β(3) and phosphorylated FAK. We propose that BDNF stimulates endothelial cell migration by a process involving TrkB/ERK/integrin α(V)β(3)/FAK, and this may help to enhance the regeneration of periodontal tissue.
authors.affiliation: Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D010766:Phosphorylation; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D039302:Integrin alphaVbeta3; D020813:Receptor, trkB; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases