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STIM2 Suppression Blocks Glial Activation to Alleviate Brain Ischemia Reperfusion Injury via Inhibition of Inflammation and Pyroptosis.
- Source :
-
Molecular biotechnology [Mol Biotechnol] 2024 Aug; Vol. 66 (8), pp. 2046-2063. Date of Electronic Publication: 2023 Aug 12. - Publication Year :
- 2024
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Abstract
- 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.<br /> (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Mice
Male
Rats
Infarction, Middle Cerebral Artery metabolism
Infarction, Middle Cerebral Artery pathology
Infarction, Middle Cerebral Artery genetics
Inflammation metabolism
Inflammation genetics
Inflammation pathology
Brain Ischemia metabolism
Brain Ischemia pathology
Brain Ischemia genetics
Mice, Inbred C57BL
PC12 Cells
Apoptosis
Disease Models, Animal
Gene Knockdown Techniques
Neuroglia metabolism
Neuroglia pathology
Microglia metabolism
Microglia pathology
Pyroptosis genetics
Reperfusion Injury metabolism
Reperfusion Injury pathology
Reperfusion Injury genetics
Stromal Interaction Molecule 2 metabolism
Stromal Interaction Molecule 2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0305
- Volume :
- 66
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 37572222
- Full Text :
- https://doi.org/10.1007/s12033-023-00823-x