PMID- 37653221
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240214
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 61
IP  - 2
DP  - 2024 Feb
TI  - TRPM7 Mediates BSCB Disruption After Spinal Cord Injury by Regulating the 
      mTOR/JMJD3 Axis in Rats.
PG  - 662-677
LID - 10.1007/s12035-023-03617-z [doi]
AB  - 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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Park, Chan Sol
AU  - Park CS
AD  - Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul, 
      02447, Republic of Korea.
AD  - Department of Biomedical Science, Kyung Hee University, Seoul, 02447, Republic of 
      Korea.
FAU - Lee, Jee Youn
AU  - Lee JY
AD  - Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul, 
      02447, Republic of Korea.
FAU - Seo, Kyung Jin
AU  - Seo KJ
AD  - Department of Biomedical Science, Kyung Hee University, Seoul, 02447, Republic of 
      Korea.
FAU - Kim, In Yi
AU  - Kim IY
AD  - Department of Biomedical Science, Kyung Hee University, Seoul, 02447, Republic of 
      Korea.
FAU - Ju, Bong Gun
AU  - Ju BG
AD  - Department of Life Science, Sogang University, Seoul, 04107, Republic of Korea.
FAU - Yune, Tae Young
AU  - Yune TY
AUID- ORCID: 0000-0001-5242-5746
AD  - Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul, 
      02447, Republic of Korea. tyune@khu.ac.kr.
AD  - Department of Biomedical Science, Kyung Hee University, Seoul, 02447, Republic of 
      Korea. tyune@khu.ac.kr.
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee 
      University, Seoul, 02447, Republic of Korea. tyune@khu.ac.kr.
AD  - Biomedical Science Institute, Kyung Hee University, Seoul, 02447, Korea. 
      tyune@khu.ac.kr.
LA  - eng
GR  - NRF-2022R1A2B5B02002106/The national research foundation of korea/
GR  - KHU-20210142/Kyung Hee University/
PT  - Journal Article
DEP - 20230901
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (TRPM Cation Channels)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - 0 (Transient Receptor Potential Channels)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *TRPM Cation Channels/metabolism
MH  - Rats, Sprague-Dawley
MH  - Matrix Metalloproteinase 2/metabolism
MH  - *Transient Receptor Potential Channels/metabolism
MH  - Endothelial Cells/metabolism
MH  - *Spinal Cord Injuries/metabolism
MH  - Spinal Cord/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Sirolimus
MH  - Blood-Brain Barrier/metabolism
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - Blood-spinal cord barrier
OT  - JMJD3
OT  - Spinal cord injury
OT  - Transient receptor potential melastatin 7 (TRPM7)
OT  - mammalian target of rapamycin (mTOR)
EDAT- 2023/09/01 00:41
MHDA- 2024/02/12 15:43
CRDT- 2023/08/31 23:37
PHST- 2023/04/19 00:00 [received]
PHST- 2023/08/27 00:00 [accepted]
PHST- 2024/02/12 15:43 [medline]
PHST- 2023/09/01 00:41 [pubmed]
PHST- 2023/08/31 23:37 [entrez]
AID - 10.1007/s12035-023-03617-z [pii]
AID - 10.1007/s12035-023-03617-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2024 Feb;61(2):662-677. doi: 10.1007/s12035-023-03617-z. Epub 2023 
      Sep 1.