期刊
NEUROBIOLOGY OF DISEASE
卷 95, 期 -, 页码 66-81出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.07.015
关键词
Blood-spinal cord barrier; Jmjd3; Matrix metalloprotease; Spinal cord injury; Tight junction
资金
- Basic Science Research Program through National Research Foundation of Korea (NRF) - Ministry of Science, ICT and future Planning [2015R1A2A2A01003795]
- grant of the Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI13C1460]
- Basic Science Research Program through NRF - Ministry of Education [2009-0093822]
- National Research Foundation of Korea [2015R1A2A2A01003795] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The disruption of the blood-spinal cord barrier (BSCB) by matrix metalloprotease (MMP) activation is a detrimental event that leads to blood cell infiltration, inflammation, and apoptosis, thereby contributing to permanent neurological disability after spinal cord injury (SCI). However, the molecular mechanisms underlying Mmp gene regulation have not been fully elucidated. Here, we demonstrated the critical role of histone H3K27 demethylase Jmjd3 in the regulation of Mmp gene expression and BSCB disruption using in vitro cellular and in vivo animal models. We found that Jmjd3 up-regulation, in cooperation with NF-kappa B, after SCI is required for Mmp-3 and Mmp-9 gene expressions in injured vascular endothelial cells. In addition, Jmjd3 mRNA depletion inhibited Mmp-3 and Mmp-9 gene expressions and significantly attenuated BSCB permeability and the loss of tight junction proteins. These events further led to improved functional recovery, along with decreased hemorrhage, blood cell infiltration, inflammation, and cell death of neurons and oligodendrocytes after SCI. Thus, our findings suggest that Jmjd3 regulation may serve as a potential therapeutic intervention for preserving BSCB integrity following SCI. (C) 2016 Elsevier Inc. All rights reserved.
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