支气管活检中哮喘相关microRNA的鉴定
2022/04/19
摘要
背景：microRNA（miRNA）表达的变化可能参与许多疾病的发病机制，包括哮喘。我们的目的是鉴定哮喘患者和健康对照者之间差异表达的miRNA，并探讨它们与哮喘临床和炎症相关参数之间的关系。
方法：对79名哮喘患者和82名健康对照者的支气管活检组织进行小RNA测序，使用线性回归模型确定差异表达的miRNA。分析差异表达的miRNA与临床和炎症性哮喘特征的相关性。使用来自相同支气管活检的mRNA数据分析潜在的miRNA-mRNA相互作用，并使用Enrichr和g:Profiler鉴定富集通路。
结果：总的来说，与对照组相比，在哮喘患者的支气管活检中发现了78个差异表达的miRNA，其中60个在控制吸烟和吸入糖皮质激素治疗后仍然存在差异表达。基于与多种临床和炎症性哮喘的相关性及负相关性，我们确定了几种与哮喘相关的miRNA，包括miR-125b-5p和miR-223-3p，受miR-125b-5p和miR-223-3p影响最丰富的生物途径是炎症反应和纤毛结构/组织。有趣的是，我们发现miR-26a-5p的低表达与血液、痰和支气管活检中检测到的更严重的嗜酸性炎症有关。
结论：总之，我们确定miR-125b-5p、miR-223-3p和miR-26a-5p可能是参与哮喘发病机制的潜在调节因子。
Identification of asthma-associated microRNAs in bronchial biopsies
Mirjam P Roffel, Ilse M Boudewijn
Abstrast
BACKGROUND：Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.
METHODS：Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA-mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler.
RESULTS：In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies.
CONCLUSION：Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
背景：microRNA（miRNA）表达的变化可能参与许多疾病的发病机制，包括哮喘。我们的目的是鉴定哮喘患者和健康对照者之间差异表达的miRNA，并探讨它们与哮喘临床和炎症相关参数之间的关系。
方法：对79名哮喘患者和82名健康对照者的支气管活检组织进行小RNA测序，使用线性回归模型确定差异表达的miRNA。分析差异表达的miRNA与临床和炎症性哮喘特征的相关性。使用来自相同支气管活检的mRNA数据分析潜在的miRNA-mRNA相互作用，并使用Enrichr和g:Profiler鉴定富集通路。
结果：总的来说，与对照组相比，在哮喘患者的支气管活检中发现了78个差异表达的miRNA，其中60个在控制吸烟和吸入糖皮质激素治疗后仍然存在差异表达。基于与多种临床和炎症性哮喘的相关性及负相关性，我们确定了几种与哮喘相关的miRNA，包括miR-125b-5p和miR-223-3p，受miR-125b-5p和miR-223-3p影响最丰富的生物途径是炎症反应和纤毛结构/组织。有趣的是，我们发现miR-26a-5p的低表达与血液、痰和支气管活检中检测到的更严重的嗜酸性炎症有关。
结论：总之，我们确定miR-125b-5p、miR-223-3p和miR-26a-5p可能是参与哮喘发病机制的潜在调节因子。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Eur Respir J, 2022 Mar 17;59(3):2101294. doi: 10.1183/13993003.01294-2021. IF: 16.671)
(Eur Respir J, 2022 Mar 17;59(3):2101294. doi: 10.1183/13993003.01294-2021. IF: 16.671)
Identification of asthma-associated microRNAs in bronchial biopsies
Mirjam P Roffel, Ilse M Boudewijn
Abstrast
BACKGROUND：Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.
METHODS：Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA-mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler.
RESULTS：In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies.
CONCLUSION：Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
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重症哮喘患者对生物制剂家庭给药的看法：一项国际定性研究
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外周血炎症表型与成人哮喘不同临床表现之间的关系：基于一项大型人群的队列研究
