Mucin gene expression during differentiation of human airway epithelia in vitro - MUC4 and MUC5B are strongly induced

Mucus hypersecretion is characteristic of chronic airway diseases. However, regulatory mechanisms are poorly understood. Human airway epithelial cells grown on permeable supports at the air-liquid interface (ALI) develop a mu cociliary morphology resembling that found in vivo. Such cultures provide a model for studying secretory cell lineage, differentiation, and function, and may provide insight regarding events leading to mucus hypersecretion. T he mucin gene expression profile of well-differentiated human airway epithe lial cells in culture has not yet been established. We compared expression of all the currently de scribed mucin genes in poorly differentiated (conve ntional cultures on plastic) and well-differentiated (ALI) human nasal and bronchial epithelial cells. Differentiation-dependent upregulation of MUC3, MUC5AC, MUC5B, and MUC6 messenger RNA (mRNA) was demonstrated using revers e transcriptase-polymerase chain reaction (RT-PCR). Northern blot analysis showed a similar increase for MUC4 and demonstrated that induction of MUC4 and MUC5B expression depended on retinoic acid. MUC1, MUC2, MUC7, and MUC8 mRNAs were also detected by RT-PCR, but these genes did not appear to be st rongly regulated as a function of differentiation. Mucin gene expression wa s similar in bronchial and nasal cells. Thus, mucociliary differentiation o f human airway epithelia in vitro entails upregulation of several mucin gen es.