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支气管平滑肌细胞外囊泡干扰哮喘患者支气管上皮的代谢和功能。

Bronchial smooth muscle extracellular vesicles interfere with bronchial epithelium metabolism and function in asthma.

作者信息

Celle Elisa, Chahin Amine, Beaufils Fabien, Cardouat Guillaume, Eyraud Edmée, Bouchet Clément, Campagnac Marilyne, Ousova Olga, Begueret Hugues, Thumerel Matthieu, Dubois Rémi, Dupuy Jean-William, Leste-Lasserre Thierry, Lacomme Sabrina, Lager-Lachaud Nina, Bellvert Floriant, Marthan Roger, Girodet Pierre-Olivier, Berger Patrick, Trian Thomas, Esteves Pauline

机构信息

Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux Proteome, TBM-Core, US5, UAR 3427, OncoProt, CIC 1401, 33000 Bordeaux, France.

INSERM, Centre de Recherche Cardio-thoracique de Bordeaux U1045, Plateforme Transcriptome Neurocentre Magendie U1215, TBM-Core, US5, UAR 3427, OncoProt, BIC, UAR 3420, 33000 Bordeaux, France.

出版信息

iScience. 2025 Apr 29;28(6):112546. doi: 10.1016/j.isci.2025.112546. eCollection 2025 Jun 20.

DOI:10.1016/j.isci.2025.112546
PMID:40487443
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12141081/
Abstract

Bronchial smooth muscle (BSM) remodeling is an important feature of severe asthma pathophysiology. We previously showed that asthmatic BSM is metabolically different and increased rhinovirus (RV) replication rate, the main trigger of severe asthma exacerbations. Extracellular vesicles (EVs) are the key mediator in cell-cell communication, but the role of BSM cells-derived EVs on bronchial epithelial has never been investigated in asthma. Using severe asthmatic and non-asthmatic tissue collection, we show that asthmatic BSM cells are able to produce a greater amount of EVs containing metabolites involved in bioenergetics. We study the bronchial epithelium energetic rewiring following stimulation with asthmatic BSM cells-derived EVs. Modifications of bronchial epithelium metabolic behavior were associated with an increased ATP production and a breakdown of bronchial epithelium barrier function such as ciliary beating frequency and efficiency. Finally, we show that asthmatic BSM cells-derived EVs increased RV replication in bronchial epithelium following RV infection.

摘要

支气管平滑肌（BSM）重塑是重度哮喘病理生理学的一个重要特征。我们之前表明，哮喘患者的支气管平滑肌在代谢上存在差异，且鼻病毒（RV）复制率增加，而鼻病毒是重度哮喘发作的主要诱因。细胞外囊泡（EVs）是细胞间通讯的关键介质，但哮喘中支气管平滑肌细胞衍生的细胞外囊泡对支气管上皮细胞的作用从未被研究过。通过收集重度哮喘患者和非哮喘患者的组织，我们发现哮喘患者的支气管平滑肌细胞能够产生更多含有参与生物能量学代谢物的细胞外囊泡。我们研究了用哮喘患者支气管平滑肌细胞衍生的细胞外囊泡刺激后支气管上皮细胞的能量重塑。支气管上皮细胞代谢行为的改变与ATP生成增加以及支气管上皮屏障功能的破坏有关，如纤毛摆动频率和效率。最后，我们表明哮喘患者支气管平滑肌细胞衍生的细胞外囊泡在RV感染后增加了支气管上皮细胞中的RV复制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/60fe456d2460/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/3b3493023eff/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/7003519e5000/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/ffafa9748157/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/5e67a3cda887/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/86c7de71a098/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/60fe456d2460/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/3b3493023eff/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/7003519e5000/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/ffafa9748157/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/5e67a3cda887/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/86c7de71a098/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b8/12141081/60fe456d2460/gr5.jpg

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本文引用的文献

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Am J Respir Crit Care Med. 2024 Oct 1;210(7):941-944. doi: 10.1164/rccm.202403-0507RL.
2
The ProteomeXchange consortium at 10 years: 2023 update.蛋白质组交换联盟成立十周年：2023 年更新。
Nucleic Acids Res. 2023 Jan 6;51(D1):D1539-D1548. doi: 10.1093/nar/gkac1040.
3
Nebulization of extracellular vesicles: A promising small RNA delivery approach for lung diseases.细胞外囊泡的雾化：一种有前途的肺部疾病小 RNA 递药方法。
J Control Release. 2022 Dec;352:556-569. doi: 10.1016/j.jconrel.2022.10.052. Epub 2022 Nov 3.
4
Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers.基于支气管重塑的潜在类别分析可预测严重学龄前喘息患儿的加重情况。
Am J Respir Crit Care Med. 2023 Feb 15;207(4):416-426. doi: 10.1164/rccm.202205-0913OC.
5
Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein.宿主琥珀酸抑制流感病毒感染通过琥珀酰化和核保留的病毒核蛋白。
EMBO J. 2022 Jun 14;41(12):e108306. doi: 10.15252/embj.2021108306. Epub 2022 May 4.
6
Asthmatic bronchial smooth muscle increases rhinovirus replication within the bronchial epithelium.哮喘患者的支气管平滑肌会增加鼻病毒在支气管上皮细胞内的复制。
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