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Endothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury
dc.contributor.authorZhang, Xuejing
dc.contributor.authorTang, Xuelian
dc.contributor.authorMa, Feifei
dc.contributor.authorFan, Yanbo
dc.contributor.authorSun, Ping
dc.contributor.authorZhu, Tianqing
dc.contributor.authorZhang, Jifeng
dc.contributor.authorHamblin, Milton H.
dc.contributor.authorChen, Y. Eugene
dc.contributor.authorYin, Ke‐jie
dc.date.accessioned2020-07-02T20:33:10Z
dc.date.availableWITHHELD_13_MONTHS
dc.date.available2020-07-02T20:33:10Z
dc.date.issued2020-07
dc.identifier.citationZhang, Xuejing; Tang, Xuelian; Ma, Feifei; Fan, Yanbo; Sun, Ping; Zhu, Tianqing; Zhang, Jifeng; Hamblin, Milton H.; Chen, Y. Eugene; Yin, Ke‐jie (2020). "Endothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury." Brain Pathology (4): 746-765.
dc.identifier.issn1015-6305
dc.identifier.issn1750-3639
dc.identifier.urihttps://hdl.handle.net/2027.42/155919
dc.description.abstractMicrovascular endothelial cell (EC) injury and the subsequent blood- brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator- activated receptor gamma (PPARγ)- mediated cerebral protection during ischemic insults needs Krüppel- like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC- targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell- selective KLF11 transgenic (EC- KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC- targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro- inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO- 1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherendothelial cell
dc.subject.otherischemic brain injury
dc.subject.otherKrüppel- like factor
dc.subject.othertight junction
dc.subject.otherblood- brain barrier
dc.titleEndothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelNeurosciences
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/1/bpa12831_am.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/2/bpa12831.pdf
dc.identifier.doi10.1111/bpa.12831
dc.identifier.sourceBrain Pathology
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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