Genes Associated with MUC5AC Expression in the Human Airway Epithelium

To help define the genes associated with mucus synthesis and secretion in the human small airway epithelium, we hypothesized that comparison of the transcriptomes of the small airway epithelium of individuals that express high vs low levels of MUC5AC, a major secretory mucin and the major component of airway mucus, could be used as a probe to identify the genes related to human small airway mucus production / secretion. Genome-wide comparison between healthy nonsmokers grouped as “high MUC5AC expressors” vs “low MUC5AC expressors” identified significantly up-regulated and down-regulated genes in the high vs low expressors. Based on the literature, genes in the up-regulated list were used to identify a 73 “MUC5AC-associated core gene” list with 9 categories: mucus components; mucus-producing cell differentiation-related transcription factor; mucus-producing cell differentiation-related pathway or mediator; post-translational modification of mucin; vesicle transport; endoplasmic reticulum stress-related; secretory granule-associated; mucus secretion-related regulator and mucus hypersecretory-related ion channel. The identification of the genes associated with increased small airway mucin production in humans should be useful in identifying therapeutic targets to treat small airway mucus hypersecretion. Since airway surface epithelial cells are the sole local source of mucus in the small airways, which are devoid of submucosal glands and mucus contributes to the morbidity and mortality of smoking-related lung diseases, especially chronic obstructive pulmonary disease (COPD), we sought to define the genes associated with mucus synthesis and secretion in the human small airway epithelium. Microarray analysis revealed 528 up-regulated and 15 down-regulated genes in MUC5AC high expressors compared to the MUC5AC low expressors. From 528 up-regulated genes, we found 73 genes with literature supported roles or potential roles in mucus production / secretion. These MUC5AC-core genes suggest that multiple molecular events involving the nucleus, endoplasmic reticulum, Golgi, vesicles and plasma membrane work coordinately in the human small airway epithelium to promote mucus production and secretion in MUC5AC-producing cells. The identification of the genes associated with increased small airway mucin production in humans should be useful in identifying therapeutic targets to treat small airway mucus hypersecretion. Samples' MUC5ACexpression status provided in supplementary file linked below. *** Note: Processed data not provided for ~86 Samples.