PMID- 37572222
OWN - NLM
STAT- Publisher
LR  - 20230812
IS  - 1559-0305 (Electronic)
IS  - 1073-6085 (Linking)
DP  - 2023 Aug 12
TI  - STIM2 Suppression Blocks Glial Activation to Alleviate Brain Ischemia Reperfusion 
      Injury via Inhibition of Inflammation and Pyroptosis.
LID - 10.1007/s12033-023-00823-x [doi]
AB  - Cerebral ischemia/reperfusion injury (CIRI) involves various pathogenic 
      mechanisms, including cytotoxicity, apoptosis, inflammation, and pyroptosis. 
      Stromal interactive molecule 2 (STIM2) is implicated in cerebral ischemia. 
      Consequently, this study investigates the biological functions of STIM2 and its 
      related mechanisms in CIRI progression. Middle cerebral artery 
      occlusion/reperfusion (MCAO/R) mouse models and oxygen-glucose 
      deprivation/reoxygenation (OGD/R) cellular models were established. STIM2 level 
      was upregulated in experimental CIRI models, as shown by reverse 
      transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting 
      and immunofluorescence staining. Brain infarction and edema were attenuated by 
      STIM2 knockdown, as 2,3,5-triphenyltetrazolium chloride (TTC) staining and brain 
      water content evaluation revealed. STIM2 knockdown relieved neuronal apoptosis, 
      microglia activation, inflammation and pyroptosis in MCAO/R mice, as detected by 
      terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, 
      enzyme-linked immunosorbent assay (ELISA) and western blotting. Results of flow 
      cytometry, ELISA, western blotting and cell counting kit-8 (CCK-8) assays also 
      showed that STIM2 knockdown inhibited inflammation, apoptosis and pyroptosis in 
      OGD/R-treated BV2 cells. Moreover, STIM2 knockdown inhibited apoptosis and 
      pyroptosis in PC12 cells incubated with conditioned medium collected from 
      OGD/R-exposed BV2 cells. Mechanistically, lncRNA Malat1 (metastasis associated 
      lung adenocarcinoma transcript 1) positively regulated STIM2 expression by 
      sponging miR-30d-5p. Their binding relationship was confirmed by luciferase 
      reporter assays. Finally, lncRNA Malat1 elevation or miR-30d-5p knockdown 
      abolished the sh-STIM2-induced inhibition in cell damage. In conclusion, STIM2 
      knockdown in microglia alleviates CIRI by inhibiting microglial activation, 
      inflammation, apoptosis, and pyroptosis.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Ye, Xihong
AU  - Ye X
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Chen, Qinyi
AU  - Chen Q
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Gong, Xingrui
AU  - Gong X
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Zhou, Chunli
AU  - Zhou C
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Yuan, Tian
AU  - Yuan T
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Wang, Xue
AU  - Wang X
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Hong, Lin
AU  - Hong L
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China.
FAU - Zhang, Jianfeng
AU  - Zhang J
AD  - Department of Anesthesiology&Institute of Neuroscience and Brain Diseases, 
      Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and 
      Science, Jingzhou Road 136, Xiangcheng District, Xiangyang, Hubei, 441021, China. 
      kmmu163@163.com.
FAU - Song, Hua
AU  - Song H
AD  - Xiangyang Maternal and Child Health Hospital, Chunyuan Road 12,Fancheng District, 
      Xiangyang, Hubei, 441021, China. 408449963@qq.com.
LA  - eng
GR  - 2022YL03B/Xiangyang City's Guiding Science and Technology Plan Project in the 
      field of medical and health care/
PT  - Journal Article
DEP - 20230812
PL  - Switzerland
TA  - Mol Biotechnol
JT  - Molecular biotechnology
JID - 9423533
SB  - IM
OTO - NOTNLM
OT  - Cerebral ischemia/reperfusion injury
OT  - Malat1
OT  - Microglia
OT  - Pyroptosis
OT  - STIM2
OT  - miR-30d-5p
EDAT- 2023/08/13 00:41
MHDA- 2023/08/13 00:41
CRDT- 2023/08/12 11:07
PHST- 2023/02/02 00:00 [received]
PHST- 2023/07/10 00:00 [accepted]
PHST- 2023/08/13 00:41 [medline]
PHST- 2023/08/13 00:41 [pubmed]
PHST- 2023/08/12 11:07 [entrez]
AID - 10.1007/s12033-023-00823-x [pii]
AID - 10.1007/s12033-023-00823-x [doi]
PST - aheadofprint
SO  - Mol Biotechnol. 2023 Aug 12. doi: 10.1007/s12033-023-00823-x.