Cell-Matrix Interactions in Gland Development in the Lung

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Abstract
The tubulo-acinar glands of the conducting airways participate in lung host defense and the pathogenesis of chronic inflammatory airway disease. Models of gland development may provide clues to mechanisms that promote hypersecretion in diseases such as chronic bronchitis and cystic fibrosis. The developmental anatomy of airway glands was described 30 years ago, but the regulation of gland formation remains a mystery. During the pseudoglandular stage of lung development, poorly differentiated surface epithelial cells grow radially from the lumen and invade the airway submucosa. The basal lamina is remodeled during this process and animal studies indicate a correlation between the expression of the 72-kD gelatinase (MMP-2) and gland morphogenesis. Cell culture models with lung epithelial and mesenchymal elements mimic early gland morphogenesis. Studies using this model have corroborated the involvement of 72-kD gelatinase in the formation of gland-like structures. While the secretion and activation of 72-kD gelatinase is correlated with epithelial matrix invasion, the presence of activated 72-kD gelatinase is not by itself sufficient to permit epithelial matrix invasion. Whether the 72-kD gelatinase participates in a more complex proteolytic cascade or whether appropriate localization of the enzyme is critical to airway epithelial morphogenesis is the focus of ongoing investigation.