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

FASEB J. 2018 Feb;32(2):935-944. doi: 10.1096/fj.201700139RRR. Epub 2018 Jan 3.

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 in monolayer 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.-Wang, Y., Wang, M.-D., Xia, Y.-P., Gao, Y., Zhu, Y.-Y., Chen, S.-C., Mao, L., He, Q.-W., Yue, Z.-Y., Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Keywords: BMECs; ischemic stroke; occludin; rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Occludin / biosynthesis*
  • Occludin / genetics
  • Oligonucleotides / pharmacology
  • Permeability
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Homeodomain Proteins
  • MIRN130 microRNA, rat
  • MicroRNAs
  • Occludin
  • Ocln protein, rat
  • Oligonucleotides