MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5

Yong Wang, Meng Die Wang, Yuan Peng Xia, Yuan Gao, Yi Yi Zhu, Sheng Cai Chen, Ling Mao, Quan Wei He, Zhen Yu Yue, Bo Hu

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells. Antagomir-130a, an antagonist of miR-130a, could attenuate brain edema, lower BBB permeability, reduce infarct volume, and improve neurologic function. MiR-130a overexpression induced by miR-130a mimic increased monolayer permeability, and intercellular inhibition of miR- 130a by a miR-130a inhibitor suppressed oxygen-glucose deprivation-induced increase inmonolayer permeability. Moreover, dual luciferase reporter system showed that Homeobox A5 was the direct target of miR-130a. MiR-130a, by inhibiting Homeobox A5 expression, could down-regulate occludin, thereby increasing BBB permeability. Our results suggested that miR-130a might be implicated in ischemia-induced BBB dysfunction and serve as a target for the treatment of ischemic stroke.

Original languageEnglish
Pages (from-to)935-944
Number of pages10
JournalFASEB Journal
Volume32
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • BMECs
  • Ischemic stroke
  • Occludin
  • Rats

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