在吸烟引起的慢性阻塞性肺病中,FUNDC1通过JNK途径促进了铁死
Yi Feng1, Jiali Weng1, Chenfei Li1
1Department of Pulmonary Medicine and Critical Care, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No.241, West Huaihai Road, Shanghai, 200030, People's Republic of China.
Lung
|September 22, 2025
概括
吸烟通过FUNDC1和JNK通路促进COPD中的铁亡. 减少FUNDC1可以防止吸烟引起的肺损伤和细胞损伤.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 烟草吸烟 (CS) 是慢性阻塞性肺病 (COPD) 的主要驱动因素,与氧化应激,线粒和铁死有关.
- 含有FUN14域的蛋白1 (FUNDC1),是一种髓受体,与COPD的发病有关.
研究的目的:
- 调查FUNDC1在COPD中CS诱导的铁亡中的作用.
- 阐明COPD中FUNDC1的潜在细胞信号传导机制.
主要方法:
- 暴露于野生型和FUNDC1敲除小鼠的CS,持续12周.
- 用CS提取物 (CSE) +/- JNK抑制剂SP6001.1治疗的FUNDC1抑制和过度表达的A549细胞.
- 评估了氧化应激,炎症,线粒体功能和铁亡.
主要成果:
- 在COPD患者的肺部和CS暴露的小鼠中,FUNDC1的表达增加.
- CS诱导肺损伤,炎症和铁亡;FUNDC1敲击减轻了这些影响.
- 在实验室和体内,FUNDC1通过JNK通路调解了CS诱导的铁死.
结论:
- 在膜上皮细胞和COPD小鼠模型中,FUNDC1在CS诱导的铁亡中至关重要.
- 该JNK-ferroptosis通路是FUNDC1在CS介导的肺损伤中的核心作用.
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