Circadian pathway is downregulated in lungs and adipose tissue in the rat model of allergic airway inflammation

Abstract

The aim of this study was to compare the transcriptome changes during allergic airway inflammation between the lungs and adipose tissue. In this study, we assessed the gene expression profile in the lungs in asthma animal model. Brown Norway rats were sensitized intranasally to house dust mite extract for 6 weeks. The control rats received PBS intranasally for the same period of time. For the transcriptome expression profiling in adipose tissue, we used Sure Print G3 Rat Gene Expression microarrays. Bioinformatic analysis was done using GeneSpring software. Pathway analysis was done in DAVID tool. Transcriptome profiling in the lungs showed that 179 genes were downregulated, whereas 217 were upregulated in allergic airway inflammation model as compared to the control rats. The downregulated genes were involved in the regulation of 4 pathways: protein processing in endoplasmic reticulum, estrogen signaling pathway, circadian rhythm and Rap1 signaling pathway. Upregulated genes were involved in 23 pathways regulation including: TNF signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction. Comparison of differentially expressed genes between lungs and adipose tissue of allergic rats, showed 31 genes deregulated in both tissues. These genes were significantly involved in the circadian pathway (adj p=0.036), neutrophil aggregation (adj p=0.005) and leukocytes cell-cell adhesion (adj p=0.048). Allergic airway inflammation affects lung transcriptome and downregulates circadian pathway not only in lungs, but also in adipose tissue. The study was supported by the National Science Centre in Poland, grant no. 2019/35/B/NZ5/02906 (A. Szczepankiewicz)