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Sci Rep. 2016 Oct 21;6:35642. doi: 10.1038/srep35642.

Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse.

Author information

1
Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
2
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, China.
3
Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China.
4
Virosis Laboratory, Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 5333 Xi An Road, Changchun, 130062, China.
5
Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg D-66421, Germany.
6
Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
7
Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.

Abstract

MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs). Silencing miR-143 increased the expression of TJPs and protected the BBB integrity against the effects of methamphetamine treatment. PUMA overexpression increased the TJP expression through a mechanism that involved the NF-κB and p53 transcription factor pathways. Mechanistically, methamphetamine mediated up-regulation of miR-143 via sigma-1 receptor with sequential activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3' kinase (PI3K)/Akt and STAT3 pathways. These results indicated that silencing miR-143 could provide a novel therapeutic strategy for BBB damage-related vascular dysfunction.

PMID:
27767041
PMCID:
PMC5073292
DOI:
10.1038/srep35642
[Indexed for MEDLINE]
Free PMC Article

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