title: Jmjd3 mediates blood-spinal cord barrier disruption after spinal cord injury by regulating MMP-3 and MMP-9 expressions.
abstract: 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-κB, 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.
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Jee Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.
authors.forename: Won H
authors.initials: WH
authors.lastname: Na
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Hae Y
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea. Electronic address: bgju@sogang.ac.kr.
authors.forename: Bong G
authors.initials: BG
authors.lastname: Ju
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: tyune@khu.ac.kr.
authors.forename: Tae Y
authors.initials: TY
authors.lastname: Yune
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002199:Capillary Permeability / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D056484:Jumonji Domain-Containing Histone Demethylases; C000655037:Kdm6b protein, rat; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Blood–spinal cord barrier; Jmjd3; Matrix metalloprotease; Spinal cord injury; Tight junction