): This proposal describes experiments to be conducted on the role of growth factors in the pathogenesis of bronchopulmonary dysplasia (BPD) in the prematurely- delivered neonatal baboon. In previous work we have described a primate model of BPD and used it to study some of the physiological and morphological changes which occur with the development of this disease. Recently, we have documented decreases in the steady state mRNAs of all surfactant proteins in this baboon homolog, correlated these changes with perturbations in morphology and physiology, and have observed a concomitant hyperplasia of type 11 cells. In addition, we have found that in conjunction with the development of neonatal lung injury there is an elevation in the amounts of TGF-A and HGF produced by lung cells. The studies in this proposal are predicated upon these findings, together with preliminary data showing that TGF-A can affect the biochemical activities of type 11 cells, and that HGF can stimulate their proliferation. These experiments will extend these observations specifically toward fetal development and its possible perturbation by premature delivery and the development of BPD. The proposed experiments are designed to accomplish the following Specific Aims: [1] To study the developmental profile of these growth factors and their receptors. [2] To determine if this pattern is altered in BPD. [3] To study the responsiveness of fetal and post-natal type 11 cells to these growth factors.
| Awasthi, S; Coalson, J J; Yoder, B A et al. (2001) Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons. Am J Respir Crit Care Med 163:389-97 |
| Vivekananda, J; Awasthi, V; Awasthi, S et al. (2000) Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism. Am J Physiol Lung Cell Mol Physiol 278:L382-92 |
| Awasthi, S; Coalson, J J; Crouch, E et al. (1999) Surfactant proteins A and D in premature baboons with chronic lung injury (Bronchopulmonary dysplasia). Evidence for an inhibition of secretion. Am J Respir Crit Care Med 160:942-9 |
