Brain-derived neurotrophic factor induces migration of endothelial cells through a TrkB-ERK-integrin αVβ3-FAK cascade
Brain-derived neurotrophic factor induces migration of endothelial cells through a TrkB-ERK-integrin αVβ3-FAK cascade
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DOI：
10.1002/jcp.22942
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发表时间：
2012-05-01
影响因子：
5.6
通讯作者：
Kurihara, Hidemi
中科院分区：
文献类型：
--
作者：
Matsuda, Shinji;Fujita, Tsuyoshi;Kurihara, Hidemi
脑源性神经营养因子（BDNF）促进牙周组织再生。由于血管生成对于组织再生非常重要，因此研究BDNF对内皮细胞功能的影响有助于揭示其促进牙周组织再生的机制。在这项研究中，我们研究了BDNF对人微血管内皮细胞（HMVECs）迁移的影响，重点是对细胞外信号调节激酶（ERK），整合素aV β 3和粘着斑激酶（FAK）的影响。采用改良的Boyden小室和伤口愈合试验评估内皮细胞的迁移。免疫印迹和免疫荧光显微镜分析整合素α V β 3的表达和ERK和FAK的磷酸化。BDNF（25 ng/ml）诱导细胞迁移。ERK抑制剂PD 98059、BDNF高亲和力受体TrkB特异性抑制剂K252 a和抗整合素aV β 3抗体抑制BDNF诱导的迁移。BDNF增加整合素aV β 3和磷酸化ERK 1/2和FAK的水平。ERK抑制剂和TrkB抑制剂还降低了整联蛋白aV β 3和磷酸化FAK的水平。我们认为BDNF通过TrkB/ERK/整合素aV β 3/FAK刺激内皮细胞迁移，这可能有助于促进牙周组织的再生。J.细胞。227：21232129，2012。(C)2011 Wiley Periodicals，Inc.
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.