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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

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

Author(s): Jianbin Sun, Tong Zhang, Chaoying Tang, Shuhang Fan, Qin Wang, Da Liu, Na Sai, Qi Ji, Weiwei Guo* and Weiju Han*

Volume 21, Issue 3, 2024

Published on: 24 June, 2024

Page: [274 - 285] Pages: 12

DOI: 10.2174/0115672026320884240620070951

Price: $65

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.

Keywords: Stria vascularis, blood-labyrinth barrier, hyperpermeability, VE-cadherin, adherens junction, noise exposure.

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