Compartment-specific transcriptomics of ozone-exposed murine lungs reveal sex- and cell type- associated perturbations relevant to mucoinflammatory lung diseases

ABSTRACT: Ozone is known to cause lung injury and resident cells of the respiratory tract, i.e., epithelial cells and macrophages, respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, complete understanding of sex-associated and cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptome profiling, we aimed to analyze gene expression alterations and biological pathways enrichment in three distinct cell type-enriched compartments of ozone-exposed murine lungs. We chronically exposed adult males and females to 0.8ppm ozone or filtered air. RNA-Seq was performed on airway epithelium-enriched airways, parenchyma, and purified airspace macrophages. Differential gene expression and biological pathway analyses were performed and supported by cellular and immunohistochemical analyses. While majority of differentially expressed genes (DEGs) in ozone-exposed versus air-exposed groups were common between both sexes, sex-specific DEGs were also identified in all the three tissue compartments. As compared to ozone-exposed males, ozone-exposed females had significant alterations in gene expression in three compartments. Pathways relevant to cell division and DNA repair were enriched in the ozone-exposed airways indicating ozone-induced airway injury and repair which was further supported by immunohistochemical analyses. In addition to cell division and DNA repair pathways, inflammatory pathways were also enriched within the parenchyma supporting contribution by both epithelial and immune cells. Finally, immune response and cytokine-cytokine receptor interactions were enriched in macrophages, indicating ozone-induced macrophage activation. Lastly, our analyses also revealed the overall upregulation of mucoinflammation and mucous cell metaplasia-associated pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE156799 | GEO | 2020/08/25

REPOSITORIES: GEO