Brain-derived neurotrophic factor induces migration of endothelial cells through a TrkB-ERK-integrin αVβ3-FAK cascade

被引:49
作者
Matsuda, Shinji [1 ]
Fujita, Tsuyoshi [1 ]
Kajiya, Mikihito [1 ]
Takeda, Katsuhiro [1 ]
Shiba, Hideki [1 ]
Kawaguchi, Hiroyuki [1 ]
Kurihara, Hidemi [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Periodontal Med, Div Frontier Med Sci,Minami Ku, Hiroshima 7348553, Japan
基金
日本学术振兴会;
关键词
NERVE GROWTH-FACTOR; FOCAL ADHESION KINASE; GENE-EXPRESSION; ACTIVATION; ANGIOGENESIS; FAMILY; RAS; PHOSPHORYLATION; REQUIREMENT; FIBRONECTIN;
D O I
10.1002/jcp.22942
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 aV beta 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 aV beta 3 and the phosphorylation of ERK and FAK were analyzed by immunoblotting and immunofluorescence microscopy. BDNF (25ng/ml) induced cell migration. PD98059, an ERK inhibitor, K252a, a specific inhibitor for TrkB, a high affinity receptor of BDNF, and an anti-integrin aV beta 3 antibody suppressed the BDNF-induced migration. BDNF increased the levels of integrin aV beta 3 and phosphorylated ERK1/2 and FAK. The ERK inhibitor and TrkB inhibitor also reduced levels of integrin aV beta 3 and phosphorylated FAK. We propose that BDNF stimulates endothelial cell migration by a process involving TrkB/ERK/integrin aV beta 3/FAK, and this may help to enhance the regeneration of periodontal tissue. J. Cell. Physiol. 227: 21232129, 2012. (C) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:2123 / 2129
页数:7
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