TRPM7 Mediates BSCB Disruption After Spinal Cord Injury by Regulating the mTOR/JMJD3 Axis in Rats.
Blood-spinal cord barrier
JMJD3
Spinal cord injury
Transient receptor potential melastatin 7 (TRPM7)
mammalian target of rapamycin (mTOR)
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
01 Sep 2023
01 Sep 2023
Historique:
received:
19
04
2023
accepted:
27
08
2023
medline:
1
9
2023
pubmed:
1
9
2023
entrez:
31
8
2023
Statut:
aheadofprint
Résumé
After spinal cord injury (SCI), secondary injuries including blood cells infiltration followed by the production of inflammatory mediators are led by blood-spinal cord barrier (BSCB) breakdown. Therefore, preventing BSCB damage could alleviate the secondary injury progresses after SCI. Recently, we reported that transient receptor potential melastatin 7 channel (TRPM7) expression is increased in vascular endothelial cells after injury and thereby mediates BSCB disruption. However, the mechanism by which TRPM7 regulates BSCB disruption has not been examined yet. In current research, we show that TRPM7 mediates BSCB disruption via mammalian target of rapamycin (mTOR) pathway after SCI in rats. After contusion injury at T9 level of spinal cord, mTOR pathway was activated in the endothelial cells of blood vessels and TRPM7 was involved in the activation of mTOR pathway. BSCB disruption, MMP-2/9 activation, and blood cell infiltration after injury were alleviated by rapamycin, a mTOR signaling inhibitor. Rapamycin also conserved the level of tight junction proteins, which were decreased after SCI. Furthermore, mTOR pathway regulated the expression and activation of histone H3K27 demethylase JMJD3, known as a key epigenetic regulator mediating BSCB damage after SCI. In addition, rapamycin inhibited JMJD3 expression, the loss of tight junction molecules, and MMP-2/9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Thus, our results suggest that TRPM7 contributes to the BSCB disruption by regulating JMJD3 expression through the mTOR pathway after SCI.
Identifiants
pubmed: 37653221
doi: 10.1007/s12035-023-03617-z
pii: 10.1007/s12035-023-03617-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : The national research foundation of korea
ID : NRF-2022R1A2B5B02002106
Organisme : Kyung Hee University
ID : KHU-20210142
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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