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

被引：107

作者：

Burek, Malgorzata ^{[1
]}

Koenig, Anna ^{[1
]}

Lang, Mareike ^{[1
]}

Fiedler, Jan ^{[2
]}

Oerter, Sabrina ^{[3
]}

Roewer, Norbert ^{[1
]}

Bohnert, Michael ^{[3
]}

Thal, Serge C. ^{[4
]}

Blecharz-Lang, Kinga G. ^{[5
,6
,7
,8
]}

Woitzik, Johannes ^{[9
,10
]}

Thum, Thomas ^{[2
]}

Foerster, Carola Y. ^{[1
]}

机构：

[1] Univ Wurzburg, Dept Anesthesia & Crit Care, Wurzburg, Germany

[2] Hannover Med Sch, IMTTS, Hannover, Germany

[3] Univ Wurzburg, Inst Forens Med, Wurzburg, Germany

[4] Johannes Gutenberg Univ Mainz, Dept Anesthesiol, Med Ctr, Mainz, Germany

[5] Charite Univ Med Berlin, Dept Expt Neurosurg, Berlin, Germany

[6] Free Univ Berlin, Berlin, Germany

[7] Humboldt Univ, Berlin, Germany

[8] Berlin Inst Hlth, Berlin, Germany

[9] Charite Univ Med Berlin, Dept Neurosurg, Berlin, Germany

[10] Charite Univ Med Berlin, Ctr Stroke Res Berlin CSB, Berlin, Germany

来源：

TRANSLATIONAL STROKE RESEARCH | 2019年 / 10卷 / 06期

关键词：

MicroRNA-212; 132; Blood-brain barrier; Tight junctions; Oxygen-glucose deprivation; Traumatic brain injury; Stroke; HIPPOCAMPAL-NEURONS; INJURY; EXPRESSION; MIGRATION; MIR-132; CLAUDIN-1; PROTECTS; MIR-212; TARGETS; MODEL;

D O I：

10.1007/s12975-018-0683-2

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：672 / 683

页数：12

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