Brain‐derived neurotrophic factor induces migration of endothelial cells through a TrkB–ERK–integrin α_Vβ₃–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.

BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia

“…If such effects also occur in pulmonary vascular smooth muscle, this could regulate vascular remodeling and potentiate the effects of hypoxia on this process. Here, it is important to note a single previous finding that BDNF enhances migration of non-pulmonary endothelial cells [47]. Again, these alternate scenarios remain to be examined.…”

Neuron-derived Neurotrophic Factor Functions as a Novel Modulator That Enhances Endothelial Cell Function and Revascularization Processes

“…Several neurotrophic factors have been reported to stimulate angiogenic responses in vascular endothelial cells (42)(43)(44)(45). For example, brain-derived neurotrophic factor induces the survival and migration of endothelial cells and stimulates angiogenesis (42,43).…”

Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

“…BDNF activates Cdc42 (Sieg et al, 2000;Yuan et al, 2003;Myers et al, 2012), a member of the Rho family of small GTPases, which further activates myosin-II via MRCK (Gomes et al, 2005;Wilkinson et al, 2005), promotes F-actin polymerization by the N-WASP-Arp2/3 pathway (Carlier et al, 1999), and enhances point-contacts dynamics (Myers and Gomez, 2011;Matsuda et al, 2012;Myers et al, 2012), all of which can enhance the contractile activity of the cell. We found that when BDNF was applied together with the Cdc42 inhibitor ML141 (10-20 µM), the enhancement of force generation induced by BDNF was markedly reduced (Fig.…”

“…For example, as an integrator and biosensor localized in adhesion sites (Mitra et al, 2005), FAK mediates the modulation of Cdc42 by extracellular guidance cues (Matsuda et al, 2012;Myers et al, 2012) and regulates cytoskeletal fluidity, GTPase activity, membrane composition, and the dynamics of focal adhesion, actin, and MTs (Mitra et al, 2005). Adhesion formation and disassembly drives the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin-II activity, and therefore adhesion dynamics .…”