Activation of Src Kinase Mediates the Disruption of Adherens Junction in the Blood-labyrinth Barrier after Acoustic Trauma.

Jianbin Sun, Tong Zhang, Chaoying Tang, Shuhang Fan, Qin Wang, Da Liu, Na Sai, Qi Ji, Weiwei Guo, Weiju Han
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Abstract

Background: Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma.

Aims: This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets.

Methods: Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blotting in C57BL/6J mice.

Results: Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction, which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase, VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated, but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair, neurotrophy and pericytes proliferation mediated by upstream VEGFR2.

Conclusion: Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.

声外伤后 Src 激酶的活化介导了血迷宫屏障粘连接头的破坏。
背景:血-迷宫屏障中的粘连接头在很大程度上尚未被研究,因为传统上认为它不如紧密连接重要。越来越多的证据表明,粘连接头实际上在紧密连接的上游发挥作用,因此粘连接头有可能成为改善声外伤等病理情况下血流-迷宫屏障渗漏的更好靶点:方法:采用免疫荧光和 Western 印迹等技术对 C57BL/6J 小鼠进行了研究:结果:噪声暴露后,血管内皮生长因子(VEGF)的上调和色素上皮衍生因子(PEDF)的下调共同激活了血管纹中的VEGF-PEDF/VEGF受体2(VEGFR2)信号通路。下游效应因子 Src 激酶随后被激活,降解 VE-cadherin,解离粘连接头,从而导致血迷宫屏障渗漏。通过抑制血管内皮生长因子受体2或Src激酶,可减轻VE-adherin降解和血迷宫屏障渗漏,但Src激酶是改善血迷宫屏障渗漏的更好靶点,因为抑制它不会干扰由上游血管内皮生长因子受体2介导的血管内皮修复神经萎缩和周细胞增殖:结论:Src 激酶可能是缓解噪声引起的粘连接头破坏和血迷宫屏障高渗透性的一个有前途的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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