Bronchial gene expression alterations associated with radiological bronchiectasis.
Bronchial gene expression alterations associated with radiological bronchiectasis.
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DOI：
10.1183/13993003.00120-2022
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发表时间：
2023-01
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影响因子：
--
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中科院分区：
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发现与放射学支气管扩张相关的气道基因表达改变可能会提高对早期支气管扩张病理生物学的理解。对173例无支气管扩张临床诊断的个体进行了放射学支气管扩张评估。对这些个体的支气管刷拭进行转录组学分析。进行单细胞去卷积以估计可能与早期疾病进展相关的细胞景观变化。20名参与者具有广泛的放射性支气管扩张（三个或更多个肺叶）。转录组学分析反映了与支气管扩张相关的生物学过程，包括参与细胞粘附的基因的表达降低和参与炎症途径的基因的表达增加（655个基因，错误发现率<0.1，log 2倍数变化>0.25）。去卷积分析表明，放射性支气管扩张与纤毛细胞和后体细胞比例增加，基底细胞比例减少有关。基因表达模式将参与者分为三组：正常，中间和支气管扩张。支气管扩张集群被参与者所富集，这些参与者具有更多的放射性支气管扩张叶（p<0.0001）、更多的症状（p=0.002）、更高的SERPINA 1突变率（p=0.03）和更高的计算机断层扫描衍生的支气管扩张评分（p<0.0001）。参与细胞粘附、Wnt信号传导、纤毛发生和干扰素-γ通路的基因在广泛放射性支气管扩张参与者的支气管中表达改变，可能与基底细胞减少和纤毛细胞增加有关。该基因表达模式不仅在具有放射性支气管扩张的个体中高度富集，而且在没有可辨别的放射性支气管扩张的个体中与气道相关症状相关，表明其反映了支气管扩张相关但非支气管扩张特异性的肺病理生理过程。在支气管上皮内，发现了与放射性支气管扩张相关的基因表达特征，表明炎症性气道环境可能与基底细胞减少但纤毛细胞增加相关https://bit.ly/3KoNXYX
Discovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis. Presence of radiological bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression. 20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log2 fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001). Genes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process. Within the bronchial epithelium, a gene expression signature associated with radiological bronchiectasis was discovered, suggesting an inflammatory airway environment that may correlate with decreased basal cells, but increased ciliated cells https://bit.ly/3KoNXYX
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影响因子：
3.1
作者：
Chandrasekaran R;Mac Aogáin M;Chalmers JD;Elborn SJ;Chotirmall SH
通讯作者：
Chotirmall SH
DOI：
10.1164/rccm.201911-2199oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
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Barbry, Pascal
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影响因子：
76.2
作者：
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O'Riordan, Thomas G.
影响因子：
4.6
作者：
Garcia, Sandra Ruiz;Deprez, Marie;Zaragosi, Laure-Emmanuelle
通讯作者：
Zaragosi, Laure-Emmanuelle