PMID- 38230623
OWN - NLM
STAT- MEDLINE
DCOM- 20240222
LR  - 20240417
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 83
IP  - 3
DP  - 2024 Feb 21
TI  - YTHDF2-regulated matrilin-3 mitigates post-reperfusion hemorrhagic transformation 
      in ischemic stroke via the PI3K/AKT pathway.
PG  - 194-204
LID - 10.1093/jnen/nlad102 [doi]
AB  - Hemorrhagic transformation can complicate ischemic strokes after recanalization 
      treatment within a time window that requires early intervention. To determine 
      potential therapeutic effects of matrilin-3, rat cerebral ischemia-reperfusion 
      was produced using transient middle cerebral artery occlusion (tMCAO); 
      intracranial hemorrhage and infarct volumes were assayed through hemoglobin 
      determination and 2,3,5-triphenyltetrazoliumchloride (TTC) staining, 
      respectively. Oxygen-glucose deprivation (OGD) modeling of ischemia was performed 
      on C8-D1A cells. Interactions between matrilin-3 and YTH N6-methyladenosine RNA 
      binding protein F2 (YTHDF2) were determined using RNA immunoprecipitation assay 
      and actinomycin D treatment. Reperfusion after tMCAO modeling increased 
      hemorrhage, hemoglobin content, and infarct volumes; these were alleviated by 
      matrilin treatment. Matrilin-3 was expressed at low levels and YTHDF2 was 
      expressed at high levels in ischemic brains. In OGD-induced cells, matrilin-3 was 
      negatively regulated by YTHDF2. Matrilin-3 overexpression downregulated 
      p-PI3K/PI3K, p-AKT/AKT, ZO-1, VE-cadherin and occludin, and upregulated p-JNK/JNK 
      in ischemic rat brains; these effects were reversed by LY294002 (a PI3K 
      inhibitor). YTHDF2 knockdown inactivated the PI3K/AKT pathway, inhibited 
      inflammation and decreased blood-brain barrier-related protein levels in cells; 
      these effects were reversed by matrilin-3 deficiency. These results indicate that 
      YTHDF2-regulated matrilin-3 protected ischemic rats against post-reperfusion 
      hemorrhagic transformation via the PI3K/AKT pathway and that matrilin may have 
      therapeutic potential in ischemic stroke.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of American 
      Association of Neuropathologists, Inc.
FAU - Chen, Hanze
AU  - Chen H
AD  - Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of 
      Medicine, Hangzhou City, Zhejiang Province, China.
FAU - Guo, Siping
AU  - Guo S
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
FAU - Li, Runnan
AU  - Li R
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
FAU - Yang, Lihui
AU  - Yang L
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
FAU - Wang, Rui
AU  - Wang R
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
FAU - Jiang, Yasi
AU  - Jiang Y
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
FAU - Hao, Yonggang
AU  - Hao Y
AD  - Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of 
      Medicine, Hangzhou City, Zhejiang Province, China.
AD  - Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou City, Jiangsu Province, China.
LA  - eng
GR  - LY19H090016/Zhejiang Provincial Natural Science Found/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Matrilin Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Transcription Factors)
RN  - 0 (Hemoglobins)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Matrilin Proteins/pharmacology/therapeutic use
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Ischemic Stroke
MH  - Signal Transduction
MH  - Rats, Sprague-Dawley
MH  - *Brain Ischemia/metabolism
MH  - Hemorrhage
MH  - Infarction, Middle Cerebral Artery/complications/drug therapy/metabolism
MH  - *Reperfusion Injury/drug therapy/metabolism
MH  - Transcription Factors
MH  - Reperfusion
MH  - Hemoglobins/pharmacology/therapeutic use
MH  - *Neuroprotective Agents/therapeutic use
PMC - PMC10880072
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Hemorrhagic transformation
OT  - Ischemic stroke
OT  - Matrilin-3
OT  - PI3K/AKT signaling pathway
OT  - YTH N6-methyladenosine RNA binding protein F2
COIS- The authors have no duality or conflicts of interest to declare.
EDAT- 2024/01/17 06:42
MHDA- 2024/02/22 06:42
PMCR- 2024/01/16
CRDT- 2024/01/17 05:54
PHST- 2024/02/22 06:42 [medline]
PHST- 2024/01/17 06:42 [pubmed]
PHST- 2024/01/17 05:54 [entrez]
PHST- 2024/01/16 00:00 [pmc-release]
AID - 7560304 [pii]
AID - nlad102 [pii]
AID - 10.1093/jnen/nlad102 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2024 Feb 21;83(3):194-204. doi: 10.1093/jnen/nlad102.