REGULATION OF MUC5 AND MUC1 GENE-EXPRESSION - CORRELATION WITH AIRWAYMUCOUS DIFFERENTIATION

The purpose of this paper was to obtain probes to study the structure and function of mucins in rat models of airway cell differentiation an d disease. We report the isolation and characterization of the rat cDN A homologue of the human airway secretory mucin, MUGS. Furthermore, we demonstrate the coordinate regulation of the expression of MUC5 and M UC1 (a membrane-bound mucin) and mucous differentiation. The rat MUC5 was cloned by the RT-PCR using motifs conserved in the secretory mucin s, MUC2 and MUC5. The rat cDNA revealed a high degree of sequence simi larity to human MUC5 (73% at the amino acid level). Alignments with th ree other secretory mucins (human MUC5, human MUC2, rat MUC2), indicat ed a conservation of the cysteines and of the octapeptide motifs, but a lack of conservation of a short tandem repeat sequence that is found only in the human MUC5. Northern analysis of MUC1 and MUGS indicated a specific tissue-restricted pattern of expression. Surprisingly, rat MUC5 exhibited a monodisperse signal, a characteristic that is unusual for most secretory mucins, including the human MUC5. Expression of MU C1 and MUC5 correlated with mucous differentiation. Both genes were ex pressed at undetectable or very low levels in undifferentiated culture s, but both mucins became strongly expressed during mucous differentia tion. Furthermore, neither mucin gene was expressed in retinoid-defici ent cultures that undergo squamous instead of mucous differentiation. These studies demonstrate that expression of MUC1 and MUC5 is coordina tely regulated with airway mucous cell differentiation. These cDNAs sh ould provide useful tools to study mucin synthesis during differentiat ion and disease.