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Volume 12
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Article

Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway

by
Lu He
1,
Rui Yin
2,
Weijian Hang
3,
Jinli Han
4,
Juan Chen
2,
Bin Wen
5,* and
Ling Chen
1,4,*
1
Division of Neonatology, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
3
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
4
Department of Pediatrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
5
Department of Clinical Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
*
Authors to whom correspondence should be addressed.
Biomedicines 2024, 12(10), 2371; https://doi.org/10.3390/biomedicines12102371
Submission received: 16 August 2024 / Revised: 29 September 2024 / Accepted: 11 October 2024 / Published: 17 October 2024
(This article belongs to the Special Issue Neuroinflammation and Neuroprotection)
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Abstract

Background: Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment. Methods: In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen–glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation. Results: H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation. Conclusions: H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.
Keywords: microglia; polarization; histone H3K9 lactylation; neonatal hypoxic–ischemic encephalopathy; neuroinflammation microglia; polarization; histone H3K9 lactylation; neonatal hypoxic–ischemic encephalopathy; neuroinflammation

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MDPI and ACS Style

He, L.; Yin, R.; Hang, W.; Han, J.; Chen, J.; Wen, B.; Chen, L. Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway. Biomedicines 2024, 12, 2371. https://doi.org/10.3390/biomedicines12102371

AMA Style

He L, Yin R, Hang W, Han J, Chen J, Wen B, Chen L. Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway. Biomedicines. 2024; 12(10):2371. https://doi.org/10.3390/biomedicines12102371

Chicago/Turabian Style

He, Lu, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, and Ling Chen. 2024. "Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway" Biomedicines 12, no. 10: 2371. https://doi.org/10.3390/biomedicines12102371

APA Style

He, L., Yin, R., Hang, W., Han, J., Chen, J., Wen, B., & Chen, L. (2024). Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway. Biomedicines, 12(10), 2371. https://doi.org/10.3390/biomedicines12102371

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