Light-dark oscillations in the lung transcriptome: Implications for lung homeostasis, repair, metabolism, disease, and drug action

Diurnal-nocturnal, or circadian-like, rhythms are 24-h variations in biological processes, evolved for the efficient functioning of living organisms. Such oscillations and their regulation in many peripheral tissues are still unclear. In this study, we used Affymetrix gene chips in a rich time-series experiment involving 54 animals killed at 18 time points within the 24-h cycle to examine light-dark cycle patterns of gene expression in rat lungs. Data mining identified 646 genes (represented by 1,006 probe sets) showing robust oscillations in expression in lung that were parsed into 8 distinct temporal clusters. Surprisingly, more than two-thirds of the probe sets showing cyclic expression peaked during the animal's light/inactive period. Six core clock genes and nine clock-related genes showed rhythmic oscillations in their expression in lung. Many of the genes that peaked during the inactive period included genes related to extracellular matrix, cytoskeleton, and protein processing and trafficking, which appear to be mainly involved in the repair and remodeling of the organ. Genes coding for growth factor ligands and their receptors, which play important roles in maintaining normal lung function, also showed rhythmic expression. In addition, genes involved in the metabolism and transport of endogenous compounds, xenobiotics, and therapeutic drugs, along with genes that are biomarkers or potential therapeutic targets for many lung diseases, also exhibited 24-h cyclic oscillations, suggesting an important role for such rhythms in regulating various aspects of the physiology and pathophysiology of lung.