Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury.
Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury.
复制标题
急性脊髓损伤后表皮生长因子通过 PI3K/Akt/Rac1 通路减轻血脊髓屏障破坏
DOI：
10.1111/jcmm.12761
复制
发表时间：
2016-06
影响因子：
5.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zheng B;Ye L;Zhou Y;Zhu S;Wang Q;Shi H;Chen D;Wei X;Wang Z;Li X;Xiao J;Xu H;Zhang H
脊髓损伤（SCI）后，血-脊髓屏障（BSCB）的破坏导致血细胞浸润，如中性粒细胞和巨噬细胞，导致永久性神经功能障碍。以往的研究表明，表皮生长因子（EGF）在SCI模型中产生有效的神经保护作用。然而，EGF是否有助于BSCB的完整性却知之甚少。本研究旨在探讨表皮生长因子（EGF）对大鼠脊髓损伤后BSCB通透性的影响及其机制。在这项研究中，我们证明，EGF管理抑制BSCB通透性的破坏，并改善SCI模型大鼠的运动活动。通过特异性抑制剂LY 294002抑制PI 3 K/Akt通路，可抑制EGF诱导的Rac 1活化以及紧密连接（TJ）和粘附连接（AJ）表达。此外，EGF对BSCB的保护作用与体内和体外Rac 1的激活有关。用Rac 1 siRNA阻断Rac 1活化下调内皮细胞中EGF诱导的TJ和AJ蛋白表达。总之，我们的结果表明，EGF治疗通过PI 3 K-Akt-Rac 1信号通路保持了BSCB的完整性并改善了SCI后的功能恢复。
After spinal cord injury (SCI), disruption of blood–spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF‐induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF‐induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K‐Akt‐Rac1 signalling pathway.