Use of transgenic mice to study autocrine-paracrine signaling in lung morphogenesis and differentiation.

Transgenic mice have been useful in demonstrating critical autocrine-paracrine interactions that are mediated by polypeptide hormones and associated receptors. These systems control interactions between the pulmonary mesenchyme and epithelium that have profound influences on lung morphogenesis, cell proliferation, and differentiation and include both inhibitory and stimulatory pathways. These pathways underlie the process of branching, sacculation, and alveolar development and may be served by several redundant polypeptides and receptors that work in concert to ensure normal pulmonary development. It is also likely that the same systems are involved in the proliferation and differentiation that accompany repair following injury. It is hoped that these transgenic models will provide insight into growth factors and receptors involved in cell proliferation, differentiation, and function during pulmonary organogenesis and also will serve to clarify the role of growth factors that may influence repair following lung injury, as seen in bronchopulmonary dysplasia and pulmonary fibrosis following severe lung injury in clinical settings.