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

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...

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Vydáno v:Translational stroke research Ročník 10; číslo 6; s. 672 - 683
Hlavní autoři: Burek, Malgorzata, König, Anna, Lang, Mareike, Fiedler, Jan, Oerter, Sabrina, Roewer, Norbert, Bohnert, Michael, Thal, Serge C., Blecharz-Lang, Kinga G., Woitzik, Johannes, Thum, Thomas, Förster, Carola Y.
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Springer US 01.12.2019
Springer Nature B.V
Témata:
Animals
Biomedical and Life Sciences
Biomedicine
Blood-Brain Barrier - metabolism
Brain Injuries, Traumatic - metabolism
Brain Injuries, Traumatic - pathology
Cardiology
Cells, Cultured
Endothelial Cells - metabolism
Ethics
Humans
Hypoxia - metabolism
Hypoxia - pathology
Invoices
Mice
MicroRNAs
MicroRNAs - metabolism
Neurology
Neurosciences
Neurosurgery
Original
Original Article
Stroke - metabolism
Stroke - pathology
Tight Junction Proteins - metabolism
Tight Junctions - metabolism
Traumatic brain injury
Vascular Surgery
Zonula Occludens-1 Protein - metabolism
Stroke
Traumatic brain injury
Blood-brain barrier
Tight junctions
MicroRNA-212/132
Oxygen-glucose deprivation
ISSN:1868-4483, 1868-601X, 1868-601X
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1868-4483
1868-601X
1868-601X
DOI:10.1007/s12975-018-0683-2