Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats

doi:10.1096/fj.201700786RR

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	Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats
	Wu, Jie-Hong 1; He, Quan-Wei 1; Wang, Xu-Xia 2; Hu, Bo 1; Lei, Hao 2; Zhou, Yi-Fan 1; Li, Ya-Nan 1; Jin, Hui-Juan 1
刊名	FASEB JOURNAL
	2018-04-01
卷号	32 期号:4 页码:2181-2196
关键词	ischemic stroke pericytes inflammatory response BBB permeability brain
ISSN号	0892-6638
DOI	10.1096/fj.201700786RR
英文摘要	The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear. To study the effect of Sema4D on BBB disruption in stroke, rats were subjected to transient middle cerebral artery occlusion and targeted injection of lentivirus-mediated clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene disruption of PlexinB1. We found that Sema4D synchronously increased with BBB permeability and accumulated in the perivascular area after stroke. Suppressing Sema4D/PlexinB1 signaling in the periinfarct cortex significantly decreased BBB permeability as detected by MRI and fibrin deposition, and thereby improved stroke outcome. In vitro, we confirmed that Sema4D disrupted BBB integrity and endothelial tight junctions. Moreover, we found that Sema4D induced pericytes to acquire a CD11b-positive phenotype and express proinflammatory cytokines. In addition, Sema4D inhibited AUF1-induced proinflammatory mRNA decay effect. Taken together, our data provides evidence that Sema4D disrupts BBB integrity and promotes an inflammatory response by binding to PlexinB1 in pericytes after transient middle cerebral artery occlusion. Our study indicates that Sema4D may be a novel therapeutic target for treatment in the acute phase of stroke.
资助项目	Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST[5001530026] ; New Century Excellent Talents in University[NCET-10-0406] ; National Natural Science Foundation of China[81571119] ; National Natural Science Foundation of China[81301002] ; National Natural Science Foundation of China[81601027] ; National Natural Science Foundation of China[81571139] ; National Natural Science Foundation of China[81301001] ; National Natural Science Foundation of China[81371311] ; National Natural Science Foundation of China[81400969] ; National Natural Science Foundation of China[81400970] ; National Research Foundation for the Doctoral Program of Higher Education of China[20120142110068] ; National Key Research and Development Program of China[2016YFC1300600]
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种	英语
出版者	FEDERATION AMER SOC EXP BIOL
WOS记录号	WOS:000429051400037
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/4937]
专题	中国科学院武汉植物园
通讯作者	Hu, Bo
作者单位	1.Huazhong Univ Sci & Technol, Union Hosp, Dept Neurol, Tongji Med Coll, 1277 Jiefang Dadao, Wuhan 430022, Hubei, Peoples R China 2.Chinese Acad Sci, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan, Wuhan, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Wu, Jie-Hong,He, Quan-Wei,Wang, Xu-Xia,et al. Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats[J]. FASEB JOURNAL,2018,32(4):2181-2196.
APA	Wu, Jie-Hong.,He, Quan-Wei.,Wang, Xu-Xia.,Hu, Bo.,Lei, Hao.,...&Jin, Hui-Juan.(2018).Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.FASEB JOURNAL,32(4),2181-2196.
MLA	Wu, Jie-Hong,et al."Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats".FASEB JOURNAL 32.4(2018):2181-2196.