在巨细胞中,颗粒物诱导的表观遗传的代谢重编码驱动慢性阻塞性肺病的发病
Myungkyung Noh1, Jeong Yeon Sim1, Jisung Kim1
1Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
Journal of hazardous materials
|November 21, 2023
概括
暴露于颗粒物会通过破坏巨细胞中的NAD+合成来触发慢性炎症和COPD. Resveratrol是一种SIRT1激活剂,可以逆转这些影响,为COPD提供一种潜在的治疗策略.
科学领域:
- 环境健康 环境健康
- 免疫学 免疫学 免疫学
- 代谢性疾病 代谢性疾病
背景情况:
- 慢性阻塞性肺病 (COPD) 与来自环境毒素的未解决的炎症有关.
- 持续暴露于颗粒物 (PM) 是一个重要的COPD风险因素,但机制尚不清楚.
- 巨细胞中心的炎症与PM诱导的COPD发展有关.
研究的目的:
- 为了阐明PM诱导的COPD发病机制.
- 研究NAD+代谢和SIRT1在PM介导炎症中的作用.
- 评估Resveratrol作为COPD的潜在治疗剂.
主要方法:
- 使用PM诱导的COPD的小鼠模型.
- 分析了 kynurenine 路径 (KP) 的巨细胞酶的转录性变化.
- 评估了CTCF的染色质结合和基因素乙化.
- 研究了白醇对炎症和COPD发展的影响.
- 检查了COPD患者的肺巨细胞.
主要成果:
- 在巨细胞中,通过CTCF结合,PM暴露降低了de novo NAD+合成酶 (HAAO,KMO,KYNU,QPRT) 的下调.
- 降低了NAD+和SIRT1的功能,导致了素乙化和促炎性基因表达的增加.
- 复星减轻了PM诱导的炎症和COPD.
- 慢性肺炎患者的基因组乙化增加和巨细胞中KP酶表达的降低.
结论:
- 不调节的NAD+代谢和SIRT1缺乏导致PM介导的COPD中的巨细胞激活.
- 向巨细胞中的代谢和表观遗传重编程是一种有前途的COPD治疗策略.
- 复星通过调节NAD+代谢和炎症来显示COPD的治疗潜力.
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