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MiR-539 Targets MMP-9 to Regulate the Permeability of Blood–Brain Barrier in Ischemia/Reperfusion Injury of Brain

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Abstract

Cerebral ischemia/reperfusion (I/R) injury severely threatens human life, while the potential mechanism underlying it is still need further exploration. The rat model of cerebral I/R injury was established using middle cerebral artery occlusion (MCAO). The rat microvascular endothelial cell line bEND.3 was exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to mimic ischemic condition in vitro. Evans blue was performed to determine the blood–brain barrier (BBB) permeability. Real-time PCR and western blot were performed to determine gene expression in mRNA and protein level, individually. Luciferase reporter assay was conducted to determine the relationship between miR-539 and MMP-9. The infarct volume and BBB permeability of cerebral (I/R) rats were significantly greater than Sham group. The expression of miR-539 was decreased, while MMP-9 was increased in the brain tissues of I/R injury rats and OGD/R pretreated bEND.3. Up-regulated miR-539 in OGD/R pretreated bEND.3 significantly promoted the BBB permeability. MiR-539 targets MMP-9 to regulate its expression. OGD/R treatment significantly promoted the BBB permeability in bEND.3, miR-539 mimic transfection abolished the effects of OGD/R, while co-transfected with pcDNA-MMP-9 abolished the effects of miR-539 mimic. MiR-539 targets MMP-9 and further regulates the BBB permeability in cerebral I/R injury.

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Authors and Affiliations

  1. Department of Interventional Neuroradiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Rd., Zhengzhou, 450000, People’s Republic of China

    Feng Fan, Jiao Yang, Yuanjie Xu & Sheng Guan

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  1. Feng Fan
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  2. Jiao Yang
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  3. Yuanjie Xu
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  4. Sheng Guan
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Correspondence to Sheng Guan.

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Fan, F., Yang, J., Xu, Y. et al. MiR-539 Targets MMP-9 to Regulate the Permeability of Blood–Brain Barrier in Ischemia/Reperfusion Injury of Brain. Neurochem Res 43, 2260–2267 (2018). https://doi.org/10.1007/s11064-018-2646-0

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  • DOI: https://doi.org/10.1007/s11064-018-2646-0

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