DIFFERENTIATION-DEPENDENT REGULATION OF RETINAL DEHYDROGENASE GENE-EXPRESSION IN THE TRACHEA

Retinoic acid (RA), a metabolite of vitamin A, is known to be a key si gnaling molecule in regulating epithelial cell differentiation. We rec ently characterized and cloned a retinal dehydrogenase (RALDH) that ca talyzes the oxidation of retinal to RA. In this study, we investigated the effects of retinoids on the level of RALDH mRNA and protein as we ll as RALDH activity in the trachea and cultured tracheal epithelial c ells. Vitamin A deficiency induced squamous metaplasia in the tracheal epithelium and down-regulated RALDH expression. Supplementation of re tinol and retinoic acid to vitamin A deficient rats restored the norma l mucociliary epithelium and up-regulated the RALDH expression. In rat epithelial cells cultured in vitro, RAinhibited squamous differentiat ion and promoted mucociliary differentiation. Squamous differentiated cultures (RA-) expressed very low levels of RALDH mRNA, wheras mucocil iary differentiated cultures (RA+) expressed high levels of RALDH mRNA . Retinal and retinol were poor inducers of mucociliary differentiatio n as well as RALDH expression. The RALDH expression paralleled the exp ression of the mucin-l gene in mucociliary cultures. These results sug gest that the expression of RALDH is dependent on the differentiation state of the airway epithelium.