MiR-98 and let-7g∗ protect the blood-brain barrier under neuroinflammatory conditions

Slava Rom, Holly Dykstra, Viviana Zuluaga-Ramirez, Nancy L. Reichenbach, Yuri Persidsky

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier 'leakiness' in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.

Original languageEnglish
Pages (from-to)1957-1965
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number12
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

Keywords

  • BBB; endothelium; inflammation; let-7g∗; miR-98

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'MiR-98 and let-7g∗ protect the blood-brain barrier under neuroinflammatory conditions'. Together they form a unique fingerprint.

Cite this