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Epidermal growth factor attenuates blood‐spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury
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 S...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882989/ https://www.ncbi.nlm.nih.gov/pubmed/26769343 http://dx.doi.org/10.1111/jcmm.12761 |
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author | Zheng, Binbin Ye, Libing Zhou, Yulong Zhu, Sipin Wang, Qingqing Shi, Hongxue Chen, Daqing Wei, Xiaojie Wang, Zhouguang Li, Xiaokun Xiao, Jian Xu, Huazi Zhang, Hongyu |
author_facet | Zheng, Binbin Ye, Libing Zhou, Yulong Zhu, Sipin Wang, Qingqing Shi, Hongxue Chen, Daqing Wei, Xiaojie Wang, Zhouguang Li, Xiaokun Xiao, Jian Xu, Huazi Zhang, Hongyu |
author_sort | Zheng, Binbin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4882989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48829892017-01-19 Epidermal growth factor attenuates blood‐spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury Zheng, Binbin Ye, Libing Zhou, Yulong Zhu, Sipin Wang, Qingqing Shi, Hongxue Chen, Daqing Wei, Xiaojie Wang, Zhouguang Li, Xiaokun Xiao, Jian Xu, Huazi Zhang, Hongyu J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2016-01-15 2016-06 /pmc/articles/PMC4882989/ /pubmed/26769343 http://dx.doi.org/10.1111/jcmm.12761 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zheng, Binbin Ye, Libing Zhou, Yulong Zhu, Sipin Wang, Qingqing Shi, Hongxue Chen, Daqing Wei, Xiaojie Wang, Zhouguang Li, Xiaokun Xiao, Jian Xu, Huazi Zhang, Hongyu Epidermal growth factor attenuates blood‐spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title | Epidermal growth factor attenuates blood‐spinal cord barrier disruption via
PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title_full | Epidermal growth factor attenuates blood‐spinal cord barrier disruption via
PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title_fullStr | Epidermal growth factor attenuates blood‐spinal cord barrier disruption via
PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title_full_unstemmed | Epidermal growth factor attenuates blood‐spinal cord barrier disruption via
PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title_short | Epidermal growth factor attenuates blood‐spinal cord barrier disruption via
PI3K/Akt/Rac1 pathway after acute spinal cord injury |
title_sort | epidermal growth factor attenuates blood‐spinal cord barrier disruption via
pi3k/akt/rac1 pathway after acute spinal cord injury |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882989/ https://www.ncbi.nlm.nih.gov/pubmed/26769343 http://dx.doi.org/10.1111/jcmm.12761 |
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