Effect of Substratum and Retinoids Upon the Mucosecretory Differentiation of Airway Epithelial Cells in Vitro

The lining of the trachea consists of a pseudostratified, mucociliary epithelium that under a variety of conditions, such as vitamin A deficiency, toxic and mechanical injury, becomes a stratified squamous epithelium. Several in vitro cell culture models have been established to study the regulation of the mucosecretory phenotype. Such studies have indicated that the mucosecretory phenotype in tracheal epithelial cells can be modulated by substratum and the presence of retinoids. Cells grown on a collagen type I gel matrix in the absence of retinoids undergo stratification and squamous cell differentiation. Cells grown on a collagen gel matrix in the presence of retinoids express a mucosecretory phenotype. As in the normal tracheal epithelium, these cultures contain columnar, polarized cells that exhibit apical tight junctions and secretory granules. Biochemical analysis of radiolabeled glycoconjugates released into the medium indicate the synthesis of mucinlike glycoproteins. Retinoids appear to determine whether tracheal epithelial cells become committed to a pathway of squamous differentiation or to a mucosecretory pathway of differentiation. The collagen gel matrix appears not to determine the commitment of the pathway of differentiation but allows the expression of the secretory phenotype in retinoic acid-treated cultures. The mechanisms by which retinoids and substratum modulate differentiation in tracheal epithelial cells is still poorly understood. It is clear that differentiation into squamous or mucous cells requires the activation and suppression of different genes. In the case of retinoids, the alterations in gene activity may be mediated by the nuclear retinoic acid receptor. In summary, in tracheal epithelial cells the substratum and extracellular matrix in conjunction with hormonal factors such as retinoids determine the ultimate function of these cells.