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Genetic Deletion of Krüppel-Like Factor 11 Aggravates Ischemic Brain Injury

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Abstract

Krüppel-like factors (KLFs) belong to the zinc finger family of transcription factors, and their function in the CNS is largely unexplored. KLF11 is a member of the KLF family, and we have previously demonstrated that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs recruitment of KLF11 as its critical coactivator. Here, we sought to determine the role of KLF11 itself in cerebrovascular function and the pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain infarction was analyzed by TTC staining. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. KLF11 KO mice exhibited significantly larger brain infarction and poorer neurological outcomes in response to ischemic insults. Genetic deficiency of KLF11 in mice also significantly aggravated ischemia-induced BBB disruption by increasing cerebrovascular permeability and edema. Mechanistically, KLF11 was found to directly regulate IL-6 in the brains of ischemic mice. These findings suggest that KLF11 acts as a novel protective factor in ischemic stroke. Elucidating the functional importance of KLF11 in ischemia may lead us to discover novel pharmacological targets for the development of effective therapies against ischemic stroke.

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Acknowledgements

This work was supported by the National Institutes of Health Grants (NS094930, NS091175, and NS086820 to K.J. Yin).

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Authors and Affiliations

  1. Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh School of Medicine, S514 BST, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Xuelian Tang, Kai Liu & Ke-Jie Yin

  2. Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu, People’s Republic of China

    Xuelian Tang & Yun Xu

  3. Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, Mailcode 8683, New Orleans, LA, 70112, USA

    Milton H. Hamblin

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  1. Xuelian Tang
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  2. Kai Liu
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Correspondence to Ke-Jie Yin.

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Tang, X., Liu, K., Hamblin, M.H. et al. Genetic Deletion of Krüppel-Like Factor 11 Aggravates Ischemic Brain Injury. Mol Neurobiol 55, 2911–2921 (2018). https://doi.org/10.1007/s12035-017-0556-9

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