Primary lung injury is a major cause of morbidity and mortality in both the preterm and term neonate. The type II alveolar epithelial cell plays a critical role in the repair of lung injury; it repopulates the entire alveolar epithelium. Interactions between the type II cells and other lung cells are important in the developing lung and in the repair of lung injury. Growth factors are a means of communication between different cell types. Transforming growth factor-beta (TGF-beta) is a growth factor that is an important regulator of growth and differentiation. The overall goal of this proposal is to study the role of TGF-beta in the developing lung and in the repair of the injured neonatal lung, focusing on the alveolar epithelium.
The specific aims of this proposal are: 1) to characterize the inhibitory effect of TGF-beta on neonatal type II epithelial cell proliferation; 2) to delineate which forms of TGF-beta are produced by the neonatal type II epithelial cell; 3) to determine if exposure to high concentration of oxygen in vivo alters the production of or response to TGF-beta by the neonatal type II epithelial cell; and 4) to determine if stage of development alters the production of or response to TGF-beta by the type II epithelial cell. These studies will test the hypothesis that interactions, important for lung injury and lung development, between type II cells and other lung cells, are mediated by TGF-beta.
| D'Angio, C T; Maniscalco, W M; Ryan, R M et al. (1999) Vascular endothelial growth factor in pulmonary lavage fluid from premature infants: effects of age and postnatal dexamethasone. Biol Neonate 76:266-73 |
| Finkelstein, J N; Horowitz, S; Sinkin, R A et al. (1992) Cellular and molecular responses to lung injury in relation to induction of tissue repair and fibrosis. Clin Perinatol 19:603-20 |
