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

文献类型：期刊论文

作者Zhou, Yi-Fan1; Li, Ya-Nan1; Jin, Hui-Juan1; Wu, Jie-Hong1; He, Quan-Wei1; Wang, Xu-Xia2; Lei, Hao2; Hu, Bo1
刊名FASEB JOURNAL
出版日期2018-04-01
卷号32期号:4页码:2181-2196
ISSN号0892-6638
关键词Ischemic Stroke Pericytes Inflammatory Response Bbb Permeability Brain
DOI10.1096/fj.201700786RR
文献子类Article
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.
WOS关键词CEREBRAL ISCHEMIA-REPERFUSION ; SEMAPHORIN 4D ; ISCHEMIA/REPERFUSION INJURY ; THERAPEUTIC TARGET ; ENDOTHELIAL-CELLS ; ARTERY OCCLUSION ; PERICYTES ; DISEASE ; SEMA4D ; PERMEABILITY
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
资助机构Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; New Century Excellent Talents in University(NCET-10-0406) ; New Century Excellent Talents in University(NCET-10-0406) ; National Natural Science Foundation of China(81571119 ; National Natural Science Foundation of China(81571119 ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Key Research and Development Program of China(2016YFC1300600) ; National Key Research and Development Program of China(2016YFC1300600) ; 81301002 ; 81301002 ; 81601027 ; 81601027 ; 81571139 ; 81571139 ; 81301001 ; 81301001 ; 81371311 ; 81371311 ; 81400969 ; 81400969 ; 81400970) ; 81400970) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; New Century Excellent Talents in University(NCET-10-0406) ; New Century Excellent Talents in University(NCET-10-0406) ; National Natural Science Foundation of China(81571119 ; National Natural Science Foundation of China(81571119 ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Key Research and Development Program of China(2016YFC1300600) ; National Key Research and Development Program of China(2016YFC1300600) ; 81301002 ; 81301002 ; 81601027 ; 81601027 ; 81571139 ; 81571139 ; 81301001 ; 81301001 ; 81371311 ; 81371311 ; 81400969 ; 81400969 ; 81400970) ; 81400970) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; New Century Excellent Talents in University(NCET-10-0406) ; New Century Excellent Talents in University(NCET-10-0406) ; National Natural Science Foundation of China(81571119 ; National Natural Science Foundation of China(81571119 ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Key Research and Development Program of China(2016YFC1300600) ; National Key Research and Development Program of China(2016YFC1300600) ; 81301002 ; 81301002 ; 81601027 ; 81601027 ; 81571139 ; 81571139 ; 81301001 ; 81301001 ; 81371311 ; 81371311 ; 81400969 ; 81400969 ; 81400970) ; 81400970) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST(5001530026) ; New Century Excellent Talents in University(NCET-10-0406) ; New Century Excellent Talents in University(NCET-10-0406) ; National Natural Science Foundation of China(81571119 ; National Natural Science Foundation of China(81571119 ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Research Foundation for the Doctoral Program of Higher Education of China(20120142110068) ; National Key Research and Development Program of China(2016YFC1300600) ; National Key Research and Development Program of China(2016YFC1300600) ; 81301002 ; 81301002 ; 81601027 ; 81601027 ; 81571139 ; 81571139 ; 81301001 ; 81301001 ; 81371311 ; 81371311 ; 81400969 ; 81400969 ; 81400970) ; 81400970)
源URL[http://ir.wipm.ac.cn/handle/112942/12916]  
专题中国科学院武汉物理与数学研究所
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		 Zhou, Yi-Fan,Li, Ya-Nan,Jin, Hui-Juan,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 Zhou, Yi-Fan.,Li, Ya-Nan.,Jin, Hui-Juan.,Wu, Jie-Hong.,He, Quan-Wei.,...&Hu, Bo.(2018).Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.FASEB JOURNAL,32(4),2181-2196.
MLA Zhou, Yi-Fan,et al."Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats".FASEB JOURNAL 32.4(2018):2181-2196.

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