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Brain‐derived neurotrophic factor induces migration of endothelial cells through a TrkB–ERK–integrin α V β 3 –FAK cascade
Author(s) -
Matsuda Shinji,
Fujita Tsuyoshi,
Kajiya Mikihito,
Takeda Katsuhiro,
Shiba Hideki,
Kawaguchi Hiroyuki,
Kurihara Hidemi
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22942
Subject(s) - tropomyosin receptor kinase b , microbiology and biotechnology , integrin , cell migration , mapk/erk pathway , focal adhesion , brain derived neurotrophic factor , angiogenesis , neurotrophic factors , chemistry , regeneration (biology) , kinase , phosphorylation , cancer research , biology , cell , receptor , biochemistry
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. J. Cell. Physiol. 227: 2123–2129, 2012. © 2011 Wiley Periodicals, Inc.