Smoking fruit flies – Impact of cigarette smoke exposure on the airway epithelium of Drosophila melanogaster

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are global epidemics with overlapping mechanisms and pathophysiologic processes. Cigarette smoking is their common major risk factor and the possibility that they are associated in the same patient is very high. Recent studies strongly suggest that CAD is common in COPD patients. However, our knowledge about the underlying molecular framework linking COPD and CAD is still fragmentary. Herein, we introduce Drosophila melanogaster, as a highly attractive model for basic COPD/CAD research. The fruit fly consists of a primitive vascular system in comparison to other invertebrate models. For example, the molecular mechanisms that regulate the formation of the tracheal tube seem to be similar to those that are involved in shaping the vascular tube in mammals.

In this study, we address the in vivo impact of cigarette smoke exposure (CSE), using 3 rd instar larvae of D. melanogaster and focused on the epithelial defense of the trachea. To identify a complete repository of genes involved in the response to cigarette smoke, we have sequenced transcriptomes of trachea after CSE by Illumina HiSeq. Our data show that the tracheal epithelium is highly responsive to smoking and that CSE triggers an immune response indicated by the expression of antimicrobial peptide genes and activation of JAK-STAT signaling along with its cytokine-like ligands upd, upd2 and upd3. Moreover, genome-wide association studies (GWASs) indicated that gene-smoking interactions in CAD are in part mediated by ADAMTS-7. ADAMTS-7 plays a crucial role in the build-up of cells in the coronary arteries, making them narrower, which finally lead to coronary heart disease. Interestingly, our RNA-seq analysis revealed that the ADAMTS-7 homologue got highly expressed in the trachea of smoke exposed animals making it an interesting candidate to further investigate its role and function.