Cigarette smoke exposure induces substantial changes in the airway epithelium of a Drosophila COPD model

Cigarette smoke with over 4000 different components is the primary risk factor of a disease called chronic obstructive pulmonary disease (COPD). COPD is predicted by the WHO to become the third leading cause of death in 2030 and already today over 64 million people suffer from it. The term COPD comprises all diseases resulting in an airflow limitation due to the destruction of lung tissue (emphysema), fibrotic changes in the lung tissue (fibrosis) and mucus hypersecretion. As there is no cure yet, the need to understand this disease in its full complexity is great, to counteract the postulated effects.

In order to understand the responses of the airway epithelium to prolonged cigarette smoke exposure (CSE), we used the fruit fly Drosophila melanogaster as a model. For this, the tracheal epithelium was subjected to CSE with smoke of three cigarettes at an interval of three hours on two consecutive days each. After manual dissection of the tracheal system, RNA sequencing and qRT-PCR was performed.

Daily low dose CSE (1 cigarette per day) reduced the lifespan of adult Drosophila significantly in comparison to matching controls. In addition, cigarette smoke exposed Drosophila larvae showed an increase in tracheal epithelial thickness. Results of RNA sequencing suggest the involvement of the Keap1/Nrf2 and JAK/STAT pathway in the reaction to CS exposure. Among the regulated genes are those encoding for the cytochrome P450 family, Glutathione S-transferases and Mucin-like proteins.

Based on these results, we will further expand the Drosophila COPD model to better understand the molecular framework underlying COPD development.