循环节障碍失调了与炎症性肺损伤相关的肺基因表达
Nancy G Casanova1, Richard L De Armond2,3, Saad Sammani2
1Department of Molecular Medicine, University of Florida Scripps Biomedical Research, Jupiter, FL, United States.
Frontiers in immunology
|April 1, 2024
概括
循环节律的破坏加剧了肺炎,并改变了小鼠的基因表达. 这种干扰会影响免疫反应和屏障完整性,这表明它是急性肺损伤的潜在治疗目标.
科学领域:
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
- 肺部病理学 肺部病理学
背景情况:
- 循环节系统调节先天免疫和细胞过程.
- 扰乱昼夜节律可能会影响免疫系统功能.
- 急性肺损伤涉及炎症反应和障碍物完整性的损害.
研究的目的:
- 研究昼夜节律失调对先天性免疫媒介肺炎的影响.
- 为了评估光引起的昼夜干扰后血管透性和基因表达的变化.
- 在改变昼夜条件下的C57BL/6J小鼠中模拟炎症性肺损伤.
主要方法:
- 使用C57BL/6J小鼠模型,通过光线曝光实现昼夜阶段转移 (CPS).
- 用于输入内脂聚糖 (LPS) 诱导肺炎.
- 在2周和10周测量了支气管支气管洗 (BAL) 蛋白质和细胞计数,组织免疫染色和差异表达基因 (DEGs).
主要成果:
- 与单独使用LPS相比,CPS与LPS结合显著增加了BAL蛋白和细胞计数.
- 在CPS-LPS暴露的肺部中鉴定了多个DEG,与昼夜干扰,肺透性和炎症 (例如Rap1信号) 有关.
- 关键的失调途径包括肌酸氨酸轻链激酶,MAP激酶和动因细胞骨调节.
结论:
- 循环节律的破坏加剧了肺部的免疫反应.
- 细胞骨基因的改变表达有助于损害上皮质和血管屏障的完整性.
- 循环节失调是急性肺损伤治疗的潜在可用药物的目标.
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