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SCAP/SREBP2-介导的胆固醇生物合成途径抑制颗粒物诱导的巨细胞激活和气道炎症
Wei-Song Chen1,2, Jia-Fei Lou1, Jie-Yu Li1
1Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Journal of inflammation research
|November 4, 2025
概括
暴露于颗粒物 (PM) 会通过改变巨细胞中的胆固醇合成引发呼吸道炎症. 对于胆固醇产生至关重要的SCAP/SREBP2通路,作为对PM诱导的炎症的保护机制.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 暴露于颗粒物 (PM) 是呼吸道疾病的重要环境风险因素.
- 巨细胞在中介呼吸道炎症中发挥着中心作用,以应对PM.
- 该SCAP/SREBP2通路调节细胞胆固醇稳态,并已涉及到各种炎症过程.
研究的目的:
- 阐明SCAP/SREBP2介导的胆固醇合成途径在巨细胞中PM诱导的呼吸道炎症中的作用.
- 研究这种途径影响巨细胞激活和对PM的炎症反应的潜在机制.
主要方法:
- 骨髓衍生的巨细胞 (BMDMs) 在体外暴露于PM,并评估了它们的细胞活性和炎症因子表达.
- RNA测序 (RNA-seq) 确定了对PM的反应中显著改变的途径.
- 使用遗传 (LysMCre-Scapf/f小鼠,siRNA) 和药理方法实现了SCAP/SREBP2通路的抑制.
- 在体内研究中使用LysMCre-Scap小鼠来模拟PM诱导的气道炎症.
主要成果:
- 巨细胞的PM细胞酶导致胆固醇水平降低,激活SCAP/SREBP2通路.
- 抑制SCAP/SREBP2或SREBP2倒退,加剧了PM诱导的炎症因子表达.
- 胆固醇生物合成的抑制加剧了PM诱导的炎症,而胆固醇补充剂减轻了炎症.
- 骨髓细胞特异性淘汰SCAP加剧了PM诱导的气道炎症和粘液产生.
结论:
- 由SCAP/SREBP2介导的胆固醇合成途径在PM引起的巨细胞激活和气道炎症中起着关键的抑制作用.
- 通过这种途径产生胆固醇是缓解PM诱导的炎症反应的关键机制.
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