Drosophila Trachea as a Novel Model of COPD

Abstract

COPD, a chronic obstructive pulmonary disease, is one of the leading causes of death worldwide. Clinical studies and research in rodent models demonstrated that failure of repair mechanisms to cope with increased ROS and inflammation in the lung leads to COPD. Despite this progress, the molecular mechanisms underlying the development of COPD remain poorly understood, resulting in a lack of effective treatments. Thus, an informative, simple model is highly valued and desired. Recently, the cigarette smoke-induced Drosophila COPD model showed a complex set of pathological phenotypes that resemble those seen in human COPD patients. The Drosophila trachea has been used as a premier model to reveal the mechanisms of tube morphogenesis. The association of these mechanisms to structural changes in COPD can be analyzed by using Drosophila trachea. Additionally, the timeline of structural damage, ROS, and inflammation can be studied in live organisms using fluorescently-tagged proteins. The related function of human COPD genes identified by GWAS can be screened using respective fly homologs. Finally, the Drosophila trachea can be used as a high-throughput drug screening platform to identify novel treatments for COPD. Therefore, Drosophila trachea is an excellent model that is complementary to rodent COPD models.

Hippo effector, Yorkie, is a Tumor Suppressor in SelectDrosophilaSquamous Epithelia

“…A pair of major tracheal tubes, termed dorsal trunks (DT), run through the entire length of the larvae—anterior-to-posterior—sending out lateral and dorsal branches that further ramify into increasingly narrower units to finally culminate in tracheoles, which deliver oxygen to the receiving cells through diffusion (Hayashi and Kondo, 2018; Sato and Kornberg, 2002; Scholl et al, 2021). The SE lining the air-filled lumen of the DT displays nuclear translocation of Yki ( Fig.…”

Modeling exercise using optogenetically contractible Drosophila larvae

“…S3 B). The tracheal system in flies is analogous to the respiratory tract or lungs that includes trachea in vertebrates [ 73 , 74 ]. It has been shown how various intensities of swimming exercise contribute to lung development and tracheal reactivity in humans and rodents, respectively [ 75 , 76 ].…”

Animals in Respiratory Research

“…The smallest tubes are called tracheoles. They lie within specific tissue cells and sit in a pool of fluid that provides a thin, moist interface for gas exchange between atmospheric air and a living cell [ 204 , 205 ]. The epithelium of the trachea consists of only one type of cell ( Figure 5 B).…”

“…The lack of an adaptive immune system becomes an advantage because there is no need to differentiate between innate and adaptive responses. Tracheae of fruit flies have been used as a screening system for drugs in the treatment of COPD [ 205 ]. Morphology, development of the tracheal system, inflammation, generation of reactive oxygen species, mobility, and lifespan can be used as readouts.…”