Regulation of Mucin and Non-Mucin Secretions and Gene Expression by Retinoic Acid in Human Airway Epithelium / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Airway hypersecretion is a frequent feature of several respiratory tract diseases including rhinitis, sinusitis, and otitis media. Efforts are being made in several laboratories to elucidate mechanisms involved in the regulation of secretion. There are several factors which modulate expression of the secretory phenotype, such as retinoic acid (RA), triiodothyronine, steroid, and extracellular matrix. We have been interested in elucidating the role of retinoids in regulating differentiation of mucin and non-mucin secretions. MATERIALS AND METHODS: Retinoic acid was removed from the culture media of normal human tracheobronchial epithelial cells grown in the air-liquid interface cultures. The effects on cell phenotype and mucin, lysozyme (LZ), and the secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. RESULTS: Removal of RA from the media induced squamous differentiation and caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes, MUC2 and MUC5AC. Lysozyme and SLPI secretions were increased in RA-depleted cultures. Paradoxically, LZ mRNA was decreased, while the SLPI mRNA levels were increased. A most intriguing finding was the paradoxical response of LZ to RA-depletion. The reason for this apparant incongruity between mRNA and protein levels is currently under investigation. CONCLUSION: Our studies show that RA is an important factor for mucous differentiation.