Hypoxia-Induced MicroRNA-212/132 Alter Blood-Brain Barrier Integrity Through Inhibition of Tight Junction-Associated Proteins in Human and Mouse Brain Microvascular Endothelial Cells.
Animals
Blood-Brain Barrier
/ metabolism
Brain Injuries, Traumatic
/ metabolism
Cells, Cultured
Endothelial Cells
/ metabolism
Humans
Hypoxia
/ metabolism
Mice
MicroRNAs
/ metabolism
Stroke
/ metabolism
Tight Junction Proteins
/ metabolism
Tight Junctions
/ metabolism
Zonula Occludens-1 Protein
/ metabolism
Blood-brain barrier
MicroRNA-212/132
Oxygen-glucose deprivation
Stroke
Tight junctions
Traumatic brain injury
Journal
Translational stroke research
ISSN: 1868-601X
Titre abrégé: Transl Stroke Res
Pays: United States
ID NLM: 101517297
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
11
06
2018
accepted:
21
12
2018
revised:
26
11
2018
pubmed:
9
1
2019
medline:
11
7
2020
entrez:
9
1
2019
Statut:
ppublish
Résumé
Blood-brain barrier (BBB) integrity is one of the important elements of central nervous system (CNS) homeostasis. MicroRNAs (miRs) have been demonstrated to play a role in many CNS disorders such as stroke and traumatic brain injury. MiR-212/132 are highly expressed in the CNS but their role at the BBB has not been characterized yet. Thus, we analyzed the expression of miR-212/132 in hypoxic mouse and human brain microvascular endothelial cells (BMEC) as well as in posttraumatic mouse and human brain tissue and serum exosomes. MiR-212/132 expression was detected in brain capillaries by in situ hybridization and was increased up to ten times in hypoxic BMEC. Over-expression of pre-miR-212/132 in BMEC decreased barrier properties and reduced migration of BMEC in the wound healing assay. We identified and validated tight junction proteins claudin-1 (Cldn1), junctional adhesion molecule 3 (Jam3), and tight junction-associated protein 1 (Tjap1) as potential miR-212/132 targets. Over-expression of miRs led to a decrease in mRNA and protein expression of Cldn1, Jam3, and Tjap1, which could be rescued by a respective anti-miR. In conclusion, our study identifies miR-212/132 as critical players at the hypoxic BBB. In addition, we propose three new direct miR-212/132 targets to be involved in miR-212/132-mediated effects on BBB properties.
Identifiants
pubmed: 30617994
doi: 10.1007/s12975-018-0683-2
pii: 10.1007/s12975-018-0683-2
pmc: PMC6842347
doi:
Substances chimiques
MIRN132 microRNA, human
0
MIRN132 microRNA, mouse
0
MIRN212 microRNA, human
0
MIRN212 microRNA, mouse
0
MicroRNAs
0
Tight Junction Proteins
0
Zonula Occludens-1 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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