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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002630-04
Application #
2210293
Study Section
Research Manpower Review Committee (MR)
Project Start
1991-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Rochester
Department
Pediatrics
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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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