Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations.

Chronic obstructive pulmonary disease (COPD) is a serious health problem. However, the molecular pathogenesis of COPD remains unknown. Here, we explored the molecular effects of cigarette smoke and bacterial infection in lung tissues of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on the COPD rats and integrated transcriptome, proteome, and metabolome data for a global view of molecular mechanisms of COPD progression. Using molecular function and pathway analyses, the genes and proteins regulated in COPD and APL-treated rats were mainly attributed to oxidoreductase, antioxidant activity, energy and fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2), and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative stress. Then, we identified the significantly regulated metabolic pathways in lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic acid, and α-linolenic acid metabolism, which belong to the lipid metabolism. In particular, we picked the arachidonic acid metabolism for a more detailed pathway analysis of transcripts, proteins, and metabolites. We could observe an increase in metabolites and genes involved in arachidonic acid metabolism in COPD rats and the decrease in these in APL-treated rats, suggesting that inflammatory responses were up-regulated in COPD rats and down-regulated in APL-treated rats. In conclusion, these system-wide results suggested that COPD progression and its treatment might be associated with oxidative stress, lipid and energy metabolism disturbance. Additionally, we demonstrated the power of integrated omics for the elucidation of genes, proteins, and metabolites' changes and disorders that were associated with COPD.