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bFGF Protects Against Oxygen Glucose Deprivation/Reoxygenation-Induced Endothelial Monolayer Permeability via S1PR1-Dependent Mechanisms

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A Correction to this article was published on 20 July 2022

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Abstract

Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R). We found that recombinant bFGF significantly decreased OGD/R-induced permeability of primary human brain microvascular endothelial cell (HBMEC) monolayer and preserved OGD/R-induced decreases of trans-endothelial electrical resistance (TEER). Western blot and immunocytochemistry showed that bFGF significantly rescued OGD/R-induced downregulation of junction proteins ZO-1, occludin, and VE-cadherin. We further show that the BBB protective effect of bFGF is via FGF receptor 1 (FGFR1) activation as FGFR1 inhibitor can block this protection effect. Moreover, we revealed that the BBB protection effect of bFGF is at least partially through rescuing the OGD/R-induced downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) protein, as S1PR1 inhibitor or SIPR1 small interfering RNA blocked the BBB protective effect of bFGF, whereas S1PR1 agonist alone has comparable BBB protection effect of bFGF. These findings will improve our understanding of the protective effect and mechanisms of bFGF on BBB and propose bFGF as a potential therapeutic agent against BBB damage in neurological disorders.

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Acknowledgements

This study was in part supported by the National Natural Science Foundation of China 81470999 (X.L.) and AHA Scientist Development Grant (SDG) 15SDG25550035 (Z.Y.).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

    Li Lin, Jian Xiao & Xiaokun Li

  2. Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA

    Li Lin, Qingzhi Wang, Kenny Qian, Zeyuan Cao, Xiaoying Wang & Zhanyang Yu

  3. Zhengzhou University First Affiliated Hospital, Zhengzhou, Henan, 450000, China

    Qingzhi Wang

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  1. Li Lin
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Contributions

LL, ZY, QW, KQ, and ZC performed the study and analyzed the data. XL and ZY designed the experiment, analyzed the data, and wrote the paper. JX and XW helped in data analysis and paper writing. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Xiaokun Li or Zhanyang Yu.

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Ethics Approval

All animal experiments were performed following the protocols approved by the Massachusetts General Hospital Animal Care and Use Committee in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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The dataset supporting the conclusions of this article is included within the article.

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The authors declare that they have no conflict of interest.

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Lin, L., Wang, Q., Qian, K. et al. bFGF Protects Against Oxygen Glucose Deprivation/Reoxygenation-Induced Endothelial Monolayer Permeability via S1PR1-Dependent Mechanisms. Mol Neurobiol 55, 3131–3142 (2018). https://doi.org/10.1007/s12035-017-0544-0

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