Journal
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 29, Issue 9, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jstrokecerebrovasdis.2020.105037
Keywords
OGD/R; MiR-139; c-Jun; Cell pyroptosis; NLRP3 inflammasome
Categories
Funding
- Scientific Research Project of Department of Education of Hunan Province [:19C1629]
- Science and Technology Project of Hengyang city [:202010031567]
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Background: Cerebral ischemia/reperfusion (I/R) injury after ischemic stroke is usually accompanied with the activation of inflammasome which seriously impairs neurological function. MiR-139 has been reported to be associated with inflammatory regulation in multiple diseases. However, its effect and mechanism on inflammation regulation after cerebral I/R injury are still poorly understood. Methods: An in vitro model of cerebral I/R injury was constructed with oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. TargetScan bioinformatics analysis and dual luciferase reporter assay were utilized to confirm the targeted relationship between miR-139 and c-Jun. Cell pyroptosis was verified by flow cytometry and Caspase-1 Detection Kit. qRT-PCR assay was performed to detect the expression levels of miR-139, c-Jun, NLRP3 and ASC. Western blotting was applied to measure the protein levels of c-Jun and pyroptosis-related markers NLRP3, ASC, caspase-1, GSDMD(Nterm). The ELISA assay was applied to measure the release of IL-1 beta, IL-18 and LDH. Results: MiR-139 was significantly downregulated whereas c-Jun was obviously upregulated after OGD/R treatment. TargetScan analysis predicted that c-Jun was a potential target of miR-139, which was verified by the dual-luciferase reporter assay. Also, overexpression of miR-139 repressed c-Jun expression. Furthermore, miR-139 inhibited OGD/R-induced cell pyroptosis and the upregulation of NLRP3, caspase-1, ASC, GSDMD(Nterm), and the release of IL-1 beta, IL-18 and LDH, while miR-139 inhibition exerted the opposite effects. However, overexpression of c-Jun aggravated OGD/R-induced nerve injury and partly abolished the neuroprotective effect of miR-139. Conclusion: Upregulation of miR-139 exerted neuroprotection against OGD/R-induced nerve injury by negatively regulating c-Jun/NLRP3 inflammasome signaling. This study offered insights for providing potential therapeutic targets for treating cerebral I/R injury. (c) 2020 Elsevier Inc. All rights reserved.
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