香烟烟雾诱导的乳费林表达的下调可以诱导COPD中的铁亡
Yuxiu Wang1, Wenjing Xu1, Kaiqi Ren1
1Department of Respiratory and Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, Jiangsu, China.
Lung
|September 23, 2025
概括
慢性阻塞性肺病 (COPD) 肺细胞中减少的乳酸 (LTF) 表达促进铁亡. 恢复LTF水平可以逆转与铁相关的细胞死亡,为COPD提供潜在的治疗见解.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 乳酸 (LTF) 对于铁平衡,免疫力和炎症至关重要.
- 香烟烟雾在慢性阻塞性肺病 (COPD) 中显著影响LTF表达.
- 在COPD中,香烟烟雾,LTF和铁代谢之间的确切机制尚未完全理解.
研究的目的:
- 阐明香烟烟雾提取物 (CSE) 调节乳酸铁素 (LTF) 的机制及其在慢性肺炎中铁代谢和铁的作用.
- 研究LTF表达对暴露于CSE的支气管上皮细胞的影响.
主要方法:
- 使用CSE在小鼠和Beas-2B细胞中构建的COPD模型.
- 在小鼠肺组织上进行了转录组和蛋白组分析.
- 利用lentivirus创建LTF过度表达和LTF干扰的细胞模型.
- 评估了细胞活力,细胞毒性,活性氧物种 (ROS),铁沉积和铁灭标志物 (ACSL4,GPX4).
- 通过传输电子显微镜检查线粒体形态.
主要成果:
- 在COPD小鼠肺组织和支气管上皮细胞中,LTF表达被下调.
- 低调的LTF与CSE暴露的支气管上皮细胞中铁的增加有关.
- LTF干扰加剧了铁亡标志物 (增加ROS,MDA;减少GSH),改变了线粒体结构,并改变了ACSL4/GPX4表达.
- 在支气管上皮细胞中,LTF过度表达逆转了CSE诱导的铁亡.
结论:
- 在CSE诱导下减少LTF表达导致支气管上皮细胞的铁积累和铁.
- 在COPD的背景下,LTF对铁死起着保护作用.
- 准LTF可能提供一种治疗策略,用于控制COPD中的铁.
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