galaktin-8 DNA 甲基化通过 MAPK / mTOR 途径调解巨细胞自,以缓解动脉样硬化
Bing Xia1, Yan-Lin Lu1, Jin Peng1,2
1School of Forensic Medicine, Guizhou Medical University, Guiyang, 550004, China.
Scientific reports
|January 2, 2025
概括
加勒-8 (GAL8) 的DNA甲基化影响动脉样硬化 (AS) 的进展. 低甲基化GAL8通过抑制巨细胞自和增加炎症来加剧AS,这表明GAL8DNA甲基化作为治疗点.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- DNA甲基化在动脉样硬化 (AS) 发病过程中至关重要.
- 加勒-8 (GAL8) DNA甲基化与冠状动脉心脏病事件有关.
- 在AS中GAL8DNA甲基化的确切机制尚不清楚.
研究的目的:
- 阐明 GAL8 DNA 甲基化和动脉样硬化中基因表达的机制.
- 研究GAL8DNA甲基化在AS进展和巨细胞行为中的作用.
- 探索针对AS治疗的GAL8DNA甲基化向潜力.
主要方法:
- 在ApoE-/-小鼠中的动脉样,用DNA甲基化抑制剂 (DO05) 和MAPK/mTOR抑制剂 (UO126) 治疗.
- 使用热测序,IHC,西部斑点和IF分析GAL8DNA甲基化,基因表达,炎症标记物 (TNF-α,MCP-1) 和自标记物 (LC3,Beclin1,p62).
- 使用针对GAL8,DO05和UO126.6的siRNAs治疗的THP-1单细胞的泡细胞模型.
主要成果:
- GAL8 DNA 低甲基化与动脉硬化病变加重,炎症增加 (MCP-1,TNF-α) 和抑制巨细胞自 (LC3 / Becklin1 减少,p62增加) 相关联.
- 抑制DNA甲基化或MAPK/mTOR途径加剧了AS,而GAL8敲击缓解了它.
- 确定了GAL8DNA甲基化作为AS的独立风险因素.
结论:
- GAL8 DNA甲基化程度与AS进展有关;低甲基化加剧AS.
- 该机制涉及调节MAPK/mTOR通路,损害巨细胞的自,并促进斑块炎症.
- 针对 GAL8 DNA 甲基化,为动脉样硬化提供了一个新的诊断和治疗策略.
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