中性粒细胞外细胞陷通过RAGE/PI3K/AKT通路促进COPD中的上皮质-介质细胞过渡
Jiawei Zou1, Lin Chen2, Yang Yang3
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China; Department of Respiratory and Critical Care Medicine, Liuzhou People's Hospital, Guangxi Medical University, Liuzhou, Guangxi, 545006, China.
中性粒细胞外细胞陷 (NETs) 通过促进上皮细胞-介质细胞过渡 (EMT) 来驱动慢性呼吸道炎症和COPD的进展. 针对NETs形成和RAGE/PI3K/AKT途径提供了潜在的COPD治疗策略.
科学领域:
- 肺部医学 肺部医学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 中性粒细胞外细胞陷 (NETs) 与慢性呼吸道炎症有关.
- NETs在慢性阻塞性肺病 (COPD) 通过表皮-介质细胞转换 (EMT) 的进展中的作用尚未完全理解.
研究的目的:
- 研究COPD患者的血清生物标志物和肺功能.
- 阐明COPD肺组织中NETs和EMT之间的关系.
- 探索香烟烟雾提取物 (CSE) 诱导的NETs对支气管上皮细胞中的EMT及其分子机制的影响.
主要方法:
- 分析了COPD患者的血清生物标志物 (DNase-I,IL-6,TNF-α,dsDNA,MPO-DNA) 和肺组织.
- 在肺组织中检查了NETs积累和EMT标记物.
- 在CSE-NETs治疗中使用了体外细胞模型 (BEAS-2B细胞).
- 研究了RAGE/PI3K/AKT信号通路.
- 使用COPD小鼠模型进行了体内研究.
主要成果:
- 慢性肺炎患者表现出血清DNase-I降低和炎症标志物升高.
- 肺组织的COPD显示增加了NETs和改变了EMT蛋白表达.
- 通过RAGE/PI3K/AKT通路激活,CSE-NETs在支气管上皮细胞中促进了EMT.
- 在小鼠模型中,DNase-I和CI-amidine通过减少NETs来减弱肺气和EMT.
结论:
- 由CSE诱导的NET在COPD的发病过程中起着至关重要的作用.
- 愤怒/PI3K/AKT信号通路是CSE-NETs诱导的EMT在COPD中的关键调解者.
- 网络和RAGE/PI3K/AKT通路代表了COPD治疗的潜在治疗点.
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