Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia.

The mucus layer that coats the airway epithelium provides a protective barrier against pathogenic and noxious agents and participates in the mucosal response to inflammation and infection. Airway mucus is composed of water, ions, lung secretions, serum protein transudates, and mucin glycoproteins (mucins). Mucins are the major components of mucus and the macromolecules that impart rheologic properties to airway mucus (1, 2). Airway mucus is overproduced in the upper and/or lower respiratory tracts during acute challenges and in chronic conditions (asthma, cystic fibrosis, bronchitis, and sinusitis), thereby contributing to mucus obstruction of the airways (3). Mucus obstruction is the culmination of several complex processes including mucin ( MUC ) gene regulation, mucin secretion and goblet cell hyperplasia (GCH) (Figure 1). Insight into each of these processes is limited; more detailed information about fundamental cellular mechanisms will be required to better understand their interrelationships. For example, pathogenic agents and inflammatory mediators initiate secretion of mucins (4–7) and sustain mucin production by increasing expression of mucin genes (8, 9). Nevertheless, each process has markedly different kinetics and their response to mediators likely involves different cellular signaling and pathways. The increasing availability of molecular probes for specific mucin genes and gene products is beginning to provide some insights into the pathogenesis of mucus overproduction. However, detailed information about the expression and regulation of respiratory tract mucins in specific disease entities is still incomplete. The report by Chen and colleagues (10) provides new information on altered expression of a specific mucin gene, MUC5B.