Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Cells. 2024 May 30;13(11):945. doi: 10.3390/cells13110945.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular cargo in the progression of COPD by identification of EV-associated protein and microRNA (miRNA) profiles. We isolated EVs from the bronchial alveolar lavage fluid (BALF) of 18 patients with COPD and 11 healthy controls using size-exclusion chromatography. EV isolates were characterized using nanoparticle tracking analysis and protein content. Proteomic analysis revealed a higher abundance of 284 proteins (log2FC > 1) and a lower abundance of 3 proteins (log2FC < -1) in EVs derived from patients with COPD. Ingenuity pathway analysis showed that proteins enriched in COPD-associated EVs trigger inflammatory responses, including neutrophil degranulation. Variances in surface receptors and ligands associated with COPD EVs suggest a preferential interaction with alveolar cells. Small RNAseq analysis identified a higher abundance of ten miRNAs and a lower abundance of one miRNA in EVs from COPD versus controls (Basemean > 100, FDR < 0.05). Our data indicate that the molecular composition of EVs in the BALF of patients with COPD is altered compared to healthy control EVs. Several components in COPD EVs were identified that may perpetuate inflammation and alveolar tissue destruction.
慢性阻塞性肺疾病（COPD）是一种无法治愈的进行性肺部疾病。越来越多的研究结果表明，细胞外囊泡（EVs）在 COPD 的发病机制中起作用。本研究旨在通过鉴定 EV 相关蛋白和 microRNA（miRNA）谱，揭示 EV 及其分子货物在 COPD 进展中的参与。我们使用排阻色谱法从 18 名 COPD 患者和 11 名健康对照者的支气管肺泡灌洗液（BALF）中分离 EV。使用纳米颗粒跟踪分析和蛋白质含量对 EV 分离物进行表征。蛋白质组学分析显示，源自 COPD 患者的 EV 中 284 种蛋白质（log2FC > 1）的丰度更高，3 种蛋白质（log2FC < -1）的丰度更低。通路分析显示，富含 COPD 相关 EV 的蛋白质触发炎症反应，包括嗜中性粒细胞脱颗粒。与 COPD EV 相关的表面受体和配体的差异表明它们与肺泡细胞的优先相互作用。小 RNAseq 分析表明，与对照组相比，COPD 患者的 EV 中存在 10 种 miRNA 的丰度增加和 1 种 miRNA 的丰度降低（Basemean > 100，FDR < 0.05）。我们的数据表明，与健康对照组 EV 相比，COPD 患者 BALF 中的 EV 分子组成发生了改变。在 COPD EV 中鉴定出几种可能持续引发炎症和肺泡组织破坏的成分。
