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Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice
Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392311/ https://www.ncbi.nlm.nih.gov/pubmed/25914628 http://dx.doi.org/10.3389/fncel.2015.00141 |
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author | Jie, Pinghui Tian, Yujing Hong, Zhiwen Li, Lin Zhou, Libin Chen, Lei Chen, Ling |
author_facet | Jie, Pinghui Tian, Yujing Hong, Zhiwen Li, Lin Zhou, Libin Chen, Lei Chen, Ling |
author_sort | Jie, Pinghui |
collection | PubMed |
description | Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema. Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO) mice. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047. The increased MMP-2/9 protein expression in hippocampi of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occludens-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein expression increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein expression was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein. |
format | Online Article Text |
id | pubmed-4392311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43923112015-04-24 Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice Jie, Pinghui Tian, Yujing Hong, Zhiwen Li, Lin Zhou, Libin Chen, Lei Chen, Ling Front Cell Neurosci Neuroscience Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema. Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO) mice. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047. The increased MMP-2/9 protein expression in hippocampi of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occludens-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein expression increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein expression was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein. Frontiers Media S.A. 2015-04-10 /pmc/articles/PMC4392311/ /pubmed/25914628 http://dx.doi.org/10.3389/fncel.2015.00141 Text en Copyright © 2015 Jie, Tian, Hong, Li, Zhou, Chen and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Jie, Pinghui Tian, Yujing Hong, Zhiwen Li, Lin Zhou, Libin Chen, Lei Chen, Ling Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title_full | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title_fullStr | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title_full_unstemmed | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title_short | Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
title_sort | blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392311/ https://www.ncbi.nlm.nih.gov/pubmed/25914628 http://dx.doi.org/10.3389/fncel.2015.00141 |
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