MODIFICATION OF MUCIN GENE-EXPRESSION IN AIRWAY DISEASE

Mucus hypersecretion is a characteristic feature of several human airway diseases, including chronic bronchitis, cystic fibrosis, and asthma. Although its pathogenesis is poorly understood, hypersecretion apparently results from the abnormally large number of mucous cells found in hypersecretory airways. The factors giving rise to these mucous cells are unknown, but experimental evidence supports possible roles for both mitosis (mucous cell hyperplasia) and differentiation (mucous cell metaplasia). On the basis of the hypothesis that differentiation would require activation of mucin mRNA transcription, we have used mucin cDNA to monitor mucin mRNA levels in an animal model of chronic bronchitis. We first showed that a mucin gene (SMUC or MUC-2) cloned from the human intestine is also expressed in the human airways and is the same or homologous to genes expressed in other human mucin-producing organs. We next showed that a homologue of the SMUC gene is expressed in several animal species, including the rat. Finally, we showed that the induction of experimental chronic bronchitis by SO2 in rats is accompanied by the induction (from near zero baseline) of airway mucin mRNA. The induction by irritants of high steady-state levels of mucin mRNA may represent one of the early events in mucous cell differentiation and hypersecretion.