Drosophila Trachea as a Novel Model of COPD.

Aaron Scholl,Istri Ndoja,Lan Jiang

doi:10.3390/ijms222312730

Aaron Scholl, Istri Ndoja + Show 1 more

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https://doi.org/10.3390/ijms222312730

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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.

Highlights

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Human Chronic obstructive pulmonary disease (COPD)-associated genes that were recently identified through genome-wide association studies (GWAS) can be screened through GWAS in the Drosophila model for their association to COPD; (4) Drosophila have been successfully used as a drug screening platform to identify novel drugs for human diseases
The Drosophila trachea can be used as a drug screening platform to identify novel treatments for COPD; (5) an increased life span can be used as a readout for the effectiveness of the manipulation, which is not suitable in most animal models

Summary

Urgent Need to Reveal Novel Mechanisms of COPD

Chronic obstructive pulmonary disease (COPD) diminishes lung function and causes breathing difficulty and is one of the leading causes of death in the United States and worldwide [1]. The Drosophila trachea provides the opportunity to observe these changes within live organisms; (2) the involved signaling pathways and cellular processes can be manipulated genetically or pharmacologically to analyze their relevance to the development of COPD phenotypes; (3) it has been estimated that over 60% of human genes associated with diseases have fly homologs [19,20]. Previous studies in Drosophila trachea have revealed genes, pathways, processes involved in tube morphogenesis The relevance of these mechanism adults is associated with clinical COPD 10 years later [93]. The current knowledge of the Drosophila adult trachea is still limited, studies of the development of air sacs provide opportunities to unveil mechanisms of COPD in relation to the disease progression in adult trachea. The morphological changes in the air sac (btlenhancer-mRFP1moesin [57]), tracheal BL (collagen IV:GFP and Perlecan:GFP [61]), and junction proteins (Dα-cat-GFP, RFP [81]) can be visualized through fluorescently-tagged structural proteins in the late pupal stage, when air sacs form

Drosophila Trachea as a Model to Reveal Novel Mechanisms of COPD

Findings

Summary