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Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury
Blood-brain barrier (BBB) damage is a critical event in ischemic stroke, contributing to aggravated brain damage. Endothelial cell form a major component of the BBB, but its regulation in stroke has yet to be clarified. We investigated the function of Yes-associated protein 1 (YAP) in the endotheliu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662521/ https://www.ncbi.nlm.nih.gov/pubmed/34899341 http://dx.doi.org/10.3389/fphar.2021.777680 |
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author | Gong, Shuaishuai Ma, Huifen Zheng, Fan Huang, Juan Zhang, Yuanyuan Yu, Boyang Li, Fang Kou, Junping |
author_facet | Gong, Shuaishuai Ma, Huifen Zheng, Fan Huang, Juan Zhang, Yuanyuan Yu, Boyang Li, Fang Kou, Junping |
author_sort | Gong, Shuaishuai |
collection | PubMed |
description | Blood-brain barrier (BBB) damage is a critical event in ischemic stroke, contributing to aggravated brain damage. Endothelial cell form a major component of the BBB, but its regulation in stroke has yet to be clarified. We investigated the function of Yes-associated protein 1 (YAP) in the endothelium on BBB breakdown during cerebral ischemia/reperfusion (I/R) injury. The effects of YAP on BBB dysfunction were explored in middle cerebral artery occlusion/reperfusion (MCAO/R)-injury model mice and using brain microvascular endothelial cells (BMEC) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. The degree of brain injury was estimated using staining (2,3,5-Triphenyltetrazolium chloride, hematoxylin and eosin) and the detection of cerebral blood flow. BBB breakdown was investigated by examining the leakage of Evans Blue dye and evaluating the expression of tight junction (TJ)-associated proteins and matrix metallopeptidase (MMP) 2 and 9. YAP expression was up-regulated in the nucleus of BMEC after cerebral I/R injury. Verteporfin (YAP inhibitor) down-regulated YAP expression in the nucleus and improved BBB hyperpermeability and TJ integrity disruption stimulated by cerebral I/R. YAP-targeted small interfering RNA (siRNA) exerted the same effects in BMEC cells exposed to OGD/R injury. Our findings provide new insights into the contributions made by YAP to the maintenance of BBB integrity and highlight the potential for YAP to serve as a therapeutic target to modulate BBB integrity following ischemic stroke and related cerebrovascular diseases. |
format | Online Article Text |
id | pubmed-8662521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86625212021-12-11 Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury Gong, Shuaishuai Ma, Huifen Zheng, Fan Huang, Juan Zhang, Yuanyuan Yu, Boyang Li, Fang Kou, Junping Front Pharmacol Pharmacology Blood-brain barrier (BBB) damage is a critical event in ischemic stroke, contributing to aggravated brain damage. Endothelial cell form a major component of the BBB, but its regulation in stroke has yet to be clarified. We investigated the function of Yes-associated protein 1 (YAP) in the endothelium on BBB breakdown during cerebral ischemia/reperfusion (I/R) injury. The effects of YAP on BBB dysfunction were explored in middle cerebral artery occlusion/reperfusion (MCAO/R)-injury model mice and using brain microvascular endothelial cells (BMEC) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. The degree of brain injury was estimated using staining (2,3,5-Triphenyltetrazolium chloride, hematoxylin and eosin) and the detection of cerebral blood flow. BBB breakdown was investigated by examining the leakage of Evans Blue dye and evaluating the expression of tight junction (TJ)-associated proteins and matrix metallopeptidase (MMP) 2 and 9. YAP expression was up-regulated in the nucleus of BMEC after cerebral I/R injury. Verteporfin (YAP inhibitor) down-regulated YAP expression in the nucleus and improved BBB hyperpermeability and TJ integrity disruption stimulated by cerebral I/R. YAP-targeted small interfering RNA (siRNA) exerted the same effects in BMEC cells exposed to OGD/R injury. Our findings provide new insights into the contributions made by YAP to the maintenance of BBB integrity and highlight the potential for YAP to serve as a therapeutic target to modulate BBB integrity following ischemic stroke and related cerebrovascular diseases. Frontiers Media S.A. 2021-11-26 /pmc/articles/PMC8662521/ /pubmed/34899341 http://dx.doi.org/10.3389/fphar.2021.777680 Text en Copyright © 2021 Gong, Ma, Zheng, Huang, Zhang, Yu, Li and Kou. https://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) and the copyright owner(s) 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 | Pharmacology Gong, Shuaishuai Ma, Huifen Zheng, Fan Huang, Juan Zhang, Yuanyuan Yu, Boyang Li, Fang Kou, Junping Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title | Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title_full | Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title_fullStr | Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title_full_unstemmed | Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title_short | Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury |
title_sort | inhibiting yap in endothelial cells from entering the nucleus attenuates blood-brain barrier damage during ischemia-reperfusion injury |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662521/ https://www.ncbi.nlm.nih.gov/pubmed/34899341 http://dx.doi.org/10.3389/fphar.2021.777680 |
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