Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury

Journal of Cellular and Molecular Medicine
Binbin ZhengHongyu Zhang

Abstract

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 signa...Continue Reading

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Citations

Feb 10, 2017·ACS Applied Materials & Interfaces·Qingqing WangJian Xiao
Mar 8, 2018·Journal of Cellular and Molecular Medicine·Jiawei LiFanghua Gong
Mar 11, 2018·Drug Delivery and Translational Research·Hiba Natsheh, Elka Touitou
Nov 28, 2019·Cell Biology International·Ning ZhuMarong Fang
Apr 25, 2020·Molecular Neurobiology·Hadi Abou-El-HassanIbrahim Omeis
Apr 10, 2020·Frontiers in Cell and Developmental Biology·Theresa C Sutherland, Cédric G Geoffroy
Dec 10, 2020·International Journal of Molecular Sciences·Jessica MaiuoloVincenzo Mollace
Dec 10, 2020·Journal of Neurotrauma·Lin-Yu JinHai-Ying Liu
Mar 24, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xishuang WangXiaoyan Wang
Jul 31, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fan BieMin Lan

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Methods Mentioned

BETA
GTPases
protein assay
transfection

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