Am. J. Respir. Cell Mol. Biol., Volume 20, Number 4, April, 1999 595-604

Mucin Gene Expression during Differentiation of Human Airway Epithelia In Vitro
MUC4 and MUC5B Are Strongly Induced

Susan H. Bernacki, Andrew L. Nelson, Lubna Abdullah, John K. Sheehan, Ann Harris, C. William Davis, and Scott H. Randell

School of Medicine, Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester; and Paediatric Molecular Genetics, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom

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 mucociliary 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. The mucin gene expression profile of well-differentiated human airway epithelial cells in culture has not yet been established. We compared expression of all the currently described mucin genes in poorly differentiated (conventional 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 reverse 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 strongly regulated as a function of differentiation. Mucin gene expression was similar in bronchial and nasal cells. Thus, mucociliary differentiation of human airway epithelia in vitro entails upregulation of several mucin genes.

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