Li Xiaopeng, Srikanthan Karthi, Rahmawati Siti Farah, Slebos Dirk-Jan, Shah Pallav L, Johnson Philip J, Kistemaker Loes E M, Nagelkerke Anika, Gosens Reinoud
Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.
Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, the Netherlands.
ERJ Open Res. 2025 May 6;11(3). doi: 10.1183/23120541.00605-2024. eCollection 2025 May.
Circadian rhythms are biological cycles that regulate various physiological processes, including immune responses, tissue repair and oxidative stress. Previous studies indicated a role for distorted circadian signalling in COPD.
In this study, we performed an unbiased analysis of the gene network that coexpressed with circadian clock signalling in COPD using weighted gene coexpression network analysis on RNA sequencing data from bronchial brushes of COPD patients.
We found that a large network of pro-inflammatory genes, including , , , and , was inversely correlated with the expression of core clock genes in bronchial brushes of COPD patients. In contrast, genes that positively coexpressed with circadian clock signalling associated with ciliated cell differentiation. Furthermore, we found that both circadian clock genes and their coexpressed genes were differentially expressed in lung tissues of COPD patients compared with healthy smokers.
Our results provide an unbiased and comprehensive analysis of the gene expression network coexpressed with circadian clock signalling in bronchial epithelium. Our findings suggest an association between circadian clock signalling and enhanced inflammatory gene expression in COPD patients.
昼夜节律是调节包括免疫反应、组织修复和氧化应激在内的各种生理过程的生物周期。先前的研究表明昼夜节律信号紊乱在慢性阻塞性肺疾病（COPD）中起作用。
在本研究中，我们使用加权基因共表达网络分析对来自COPD患者支气管刷检的RNA测序数据进行了与COPD中昼夜节律信号共表达的基因网络的无偏分析。
我们发现包括[此处应有具体基因名称但未给出]等在内的一大类促炎基因网络与COPD患者支气管刷检中核心生物钟基因的表达呈负相关。相比之下，与昼夜节律信号正共表达的基因与纤毛细胞分化相关。此外，我们发现与健康吸烟者相比，COPD患者肺组织中昼夜节律生物钟基因及其共表达基因均有差异表达。
我们的结果提供了对支气管上皮中与昼夜节律信号共表达的基因表达网络的无偏且全面的分析。我们的发现提示COPD患者中昼夜节律信号与炎症基因表达增强之间存在关联。
