Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen
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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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504212/pdf/","citationCount":"0","resultStr":"{\"title\":\"Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway.\",\"authors\":\"Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen\",\"doi\":\"10.3390/biomedicines12102371\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). 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引用次数: 0
摘要
背景:缺氧诱导的小胶质细胞 M1 极化和由此产生的炎症参与了缺氧缺血性脑病(HIE)造成的损害。组蛋白乳酰化是一种新型表观遗传修饰,即在赖氨酸残基上添加乳酸,可能在 HIE 发病机制中发挥作用。本研究探讨了组蛋白乳酰化在缺氧诱导的M1小胶质细胞极化和炎症中的作用,旨在为HIE的治疗提供启示:在这项研究中,我们利用HIE动物模型和氧-葡萄糖剥夺细胞模型评估了缺氧对小胶质细胞极化的影响。通过 Western 印迹法检测了不同赖氨酸残基上的组蛋白乳酰化。通过免疫荧光、qPCR 和 Western 印迹分析了小胶质细胞极化和炎性细胞因子。利用 RNA 测序、ChIP-qPCR 和 siRNA 阐明了 H3K9 乳化的机制:结果:在M1极化过程中,细胞质乳酸导致H3K9乳酸化增加。抑制 P300 或减少乳酸脱氢酶 A 的表达可减少 H3K9 乳化,从而抑制 M1 极化。转录组分析表明,H3K9 乳酰化通过 TNF 信号通路调控 M1 极化。ChIP-qPCR证实H3K9乳酰化富集于TNFα位点,促进了OGD诱导的M1极化和炎症:结论:H3K9乳酰化通过TNF通路促进M1极化和炎症,是新生儿HIE的潜在治疗靶点。
Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway.
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.
BiomedicinesBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.20
自引率
8.50%
发文量
2823
审稿时长
8 weeks
期刊介绍:
Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.