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MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation.

Lopez-Ramirez, Miguel Alejandro; Wu, Dongsheng; Pryce, Gareth; Simpson, Julie E.; Reijerkerk, Arie; King-Robson, Josh; Kay, Oliver; de Vries, Helga E.; Hirst, Mark C.; Sharrack, Basil; Baker, David; Male, David Kingsley; Michael, Gregory J. and Romero, Ignacio Andres (2014). MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. FASEB Journal, 28(6) pp. 2551–2565.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1096/fj.13-248880
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Abstract

Blood-brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular dysfunction during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of pathogenic responses, although their role in central nervous system (CNS) microvascular disorders is largely unknown. We have identified miR-155 as a critical miRNA in neuroinflammation at the BBB. miR-155 is expressed at the neurovascular unit of individuals with MS and of mice with experimental autoimmune encephalomyelitis (EAE). In mice, loss of miR-155 reduced CNS extravasation of systemic tracers, both in EAE and in an acute systemic inflammation model induced by lipopolysaccharide. In cultured human brain endothelium, miR-155 was strongly and rapidly upregulated by inflammatory cytokines. miR-155 up-regulation mimicked cytokine-induced alterations in junctional organization and permeability, whereas inhibition of endogenous miR-155 partially prevented a cytokine-induced increase in permeability. Furthermore, miR-155 modulated brain endothelial barrier function by targeting not only cell-cell complex molecules such as annexin-2 and claudin-1, but also focal adhesion components such as DOCK-1 and syntenin-1. We propose that brain endothelial miR-155 is a negative regulator of BBB function that may constitute a novel therapeutic target for CNS neuroinflammatory disorders.

Item Type: Journal Item
Copyright Holders: 2014 FASEB
ISSN: 1530-6860
Keywords: multiple sclerosis; neurovascular dysfunction; junctional complex molecules; focal adhesion
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Research Group: Innovation, Knowledge & Development research centre (IKD)
Item ID: 42437
Depositing User: Ignacio A Romero
Date Deposited: 14 Apr 2015 08:48
Last Modified: 22 May 2019 13:42
URI: http://oro.open.ac.uk/id/eprint/42437
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