A network of pro-inflammatory genes repressed by clock signalling in bronchial epithelium

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 CXCL8, IL1B, IL1A, CSF1 and TGFB1, 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.