Cilia Plays a Pivotal Role in the Hypersecretion of Airway Mucus in Mice.

Background: Airway mucus hypersecretion is a prominent pathophysiological characteristic observed in chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma. It is a significant risk factor for lung dysfunction and impaired quality of life. Therefore, it is crucial to investigate changes in the major genes expressed in the lungs during airway mucus hypersecretion. Such investigations can help to identify genetic targets for the development of effective treatments to manage airway mucus hypersecretion and improve clinical outcomes for those affected by these respiratory disorders.

Objective: Our study aims to identify changes in the expression of key genes in the lungs during airway mucus hypersecretion in mice.

Methods: Thirty male C57BL/6 mice were randomly allocated into two groups. The Pyocyanin (PCN) group was intranasally infected with 25 μl of pyocyanin solution (1 μg/μl), while the phosphate-buffered saline (PBS) group received 25 μl of PBS intranasally once daily. The lung tissue of mice was extracted after 21 days for the purpose of identifying causal genes through a combination of transcriptomic and proteomic analysis. Finally, we validated the differentially expressed proteins using qRT-PCR and western blot.

Results: Our findings revealed significant alterations in 35,268 genes and 7,004 proteins within the lung tissue of mice treated with PCN. Pathway enrichment analysis, utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, showed that the differentially expressed proteins were mainly associated with apoptosis, galactose metabolism, and asthma, among the overlapping genes and proteins. To validate the results of the transcriptomic and proteomic analyses, we used qRT-PCR to examine the expression levels of fourteen differentially expressed proteins (DEPs), namely Fpr1, Ear1, Lama3, Col19a1, Spag16, Ropn1l, Dnali1, Cfap70, Ear2, Drc1, Ifit3, Lrrc23, Slpi, and Fam166b. Subsequently, we confirmed the expression of Spag16, Dnali1, and Ropn1l by western blotting.

Conclusions: Our study identified three DEPs, namely Spag16, Dnali1, and Ropn1l, which are closely associated with the movement and organization of cilia. This study provides novel insights for the development of therapeutic interventions targeting airway mucus hypersecretion.