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...

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Autores principales:	Shuaishuai Gong, Huifen Ma, Fan Zheng, Juan Huang, Yuanyuan Zhang, Boyang Yu, Fang Li, Junping Kou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	YAP verteporfin endothelial cells blood-brain barrier ischemic stroke Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9e45336b887e4d97af46ae224f8c90d5
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spelling	oai:doaj.org-article:9e45336b887e4d97af46ae224f8c90d52021-12-01T07:40:15ZInhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury1663-981210.3389/fphar.2021.777680https://doaj.org/article/9e45336b887e4d97af46ae224f8c90d52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.777680/fullhttps://doaj.org/toc/1663-9812Blood-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.Shuaishuai GongHuifen MaFan ZhengJuan HuangYuanyuan ZhangBoyang YuFang LiJunping KouFrontiers Media S.A.articleYAPverteporfinendothelial cellsblood-brain barrierischemic strokeTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	YAP verteporfin endothelial cells blood-brain barrier ischemic stroke Therapeutics. Pharmacology RM1-950
spellingShingle	YAP verteporfin endothelial cells blood-brain barrier ischemic stroke Therapeutics. Pharmacology RM1-950 Shuaishuai Gong Huifen Ma Fan Zheng Juan Huang Yuanyuan Zhang Boyang Yu Fang Li Junping Kou Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury
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	article
author	Shuaishuai Gong Huifen Ma Fan Zheng Juan Huang Yuanyuan Zhang Boyang Yu Fang Li Junping Kou
author_facet	Shuaishuai Gong Huifen Ma Fan Zheng Juan Huang Yuanyuan Zhang Boyang Yu Fang Li Junping Kou
author_sort	Shuaishuai Gong
title	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_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_sort	inhibiting yap in endothelial cells from entering the nucleus attenuates blood-brain barrier damage during ischemia-reperfusion injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9e45336b887e4d97af46ae224f8c90d5
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Inhibiting YAP in Endothelial Cells From Entering the Nucleus Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury

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