Abstracto

Smooth muscle proliferation is stimulated by the airway epithelium

Reynold A Panettieri

Chronic tissue injury and inflammation triggered by exogenous stimuli can cause acute bronchoconstriction. Over time, structural changes such as goblet cell hyperplasia, subepithelial fibrosis, smooth muscle cell hypertrophy and hyperplasia, and increased vascularity and edema occur in the airway wall (airway remodeling). An intensive effort is aimed at understanding the mechanisms that lead to airway remodeling, in hopes of not only slowing, but perhaps reversing, the structural alterations. Airway epithelial cells play a critical role in the defense system of the lungs by providing an important barrier function to potentially toxic environmental agents that can promote epithelial damage, or induce bronchoconstriction in susceptible individuals. Not surprisingly, epithelial shedding, marked by increased numbers of epithelial cell clumps (creola bodies) in sputum and bronchial epithelium desquamation, are features of airway injury. The sequelae is an airway epithelium in a chronic state of wound repair, which secretes soluble mediators (e.g., IGF) necessary for cell proliferation, migration, and extracellular matrix synthesis consistent with a healing wound environment. Communication between the epithelium and the underlying fibroblast in the lamina propria is prevalent and normal during fetal lung development. In contrast, the airway smooth muscle lies adjacent to the lamina propria, and therefore a further distance from the epithelium. For the epithelium to influence smooth muscle cell behavior, soluble mediators would need to diffuse through the lamina propria. Hence, the vast majority of investigation has focused on the role of the epithelium in subepithelial fibrosis. Although progress has been made in identifying mitogenic stimuli of airway smooth muscle, the potential role of epithelium-derived mediators in smooth muscle proliferation remains unexplored.