通过调节DNA损伤和DNA损伤反应,ATM参与细颗粒物诱导的气道炎症
Yan Jin1,2, Yiting Li1, Shiyi He1
1Department of Respiratory and Critical Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Environmental toxicology
|July 24, 2023
概括
细颗粒物 (PM2.5) 暴露会引发气道炎症,导致DNA损伤并激活DNA损伤修复 (DDR) 途径. 该ATM基因促进这种炎症,建议它.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 颗粒物 (PM2.5) 与慢性呼吸道疾病 (如COPD和喘) 有关.
- 由于PM2.5引起的呼吸道炎症的确切机制尚未完全理解.
- DNA损伤和修复途径与炎症反应有关.
研究的目的:
- 调查ATM基因在PM2.5引起的气道炎症中的作用.
- 为了阐明DNA损伤和DNA损伤修复 (DDR) 在PM2.5暴露中的参与.
- 探索针对ATM在管理PM2.5相关的呼吸道疾病的治疗潜力.
主要方法:
- 在体内研究中,使用暴露于PM2.5.5的Ataxia telangiectasia突变异构体 (ATM+/-) 和野生型 (WT) 老鼠.
- 在实验室中使用人类支气管上皮细胞 (HBE) 的研究,通过siRNA进行ATM基因下调.
- 对炎症标记物 (中性粒细胞,CXCL-1,TNF-α,CXCL-2) 和DNA损伤/修复蛋白 (FANCD2,FANCI) 的分析.
主要成果:
- 与ATM+/-小鼠相比,在WT小鼠中,暴露于PM2.5导致中性粒细胞和CXCL-1增加.
- 在HBE细胞中ATM的下调减少了PM2.5暴露后TNF-α,CXCL-1和CXCL-2的表达.
- 由于ATM缺乏或下调减弱了PM2.5引起的气道炎症和DDR标志物表达.
结论:
- ATM在PM2.5引起的气道炎症中起着促进作用.
- 通过ATM调节DNA损伤和DDR,有助于PM2.5引起的气道炎症.
- 针对ATM可能为缓解PM2.5相关的呼吸道疾病提供一种新的策略.
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