METTL14 regulates microglia/macrophage polarization and NLRP3 inflammasome activation after ischemic stroke by the KAT3B-STING axis

Yamei Li; Jiacen Li; Qian Yu; Ling Ji; Bo Peng

Neurobiology of Disease (Sep 2023)

METTL14 regulates microglia/macrophage polarization and NLRP3 inflammasome activation after ischemic stroke by the KAT3B-STING axis

Yamei Li,
Jiacen Li,
Qian Yu,
Ling Ji,
Bo Peng

Affiliations

Yamei Li: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China
Jiacen Li: Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Sichuan, China
Qian Yu: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China
Ling Ji: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China; Corresponding authors at: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 West Second Section, First Ring Road, Chengdu 610072, China.
Bo Peng: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China; Corresponding authors at: Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 West Second Section, First Ring Road, Chengdu 610072, China.

Journal volume & issue: Vol. 185
p. 106253

Abstract

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N6-methyladenosine (m6A) plays a crucial role in ischemic stroke, whereas the role of methyltransferase-like 14 (METTL14) in ischemic stroke remains unknown. A model of middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation/reperfusion (OGD/R) model in HAPI cells were used to simulate ischemic stroke in vivo and in vitro. We found that METTL14 level was upregulated in microglia/macrophage after MCAO and OGD/R. METTL14 enhanced the expression of KAT3B by promoting the m6A modification of KAT3B mRNA. STING has been identified as a target for KAT3B and KAT3B increased STING expression by enhancing H3K27ac in the STING promoter. METTL14 promoted M1 polarization and NLRP3 inflammasome/pyroptosis axis by the KAT3B-STING signaling after OGD/R. METTL14 depletion relieved brain injury by inhibiting M1-like microglia/macrophage polarization and NLRP3 inflammasome/pyroptosis axis in MCAO rats. These findings indicate that METTL14 depletion relieves MCAO-induced brain injury, probably via switching microglia/macrophage from M1 towards M2 and restraining NLRP3 inflammasome/pyroptosis axis in microglia/macrophage.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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