During late fetal development, the lung must prepare for the transition to air breathing. Maintaining alveolar stability becomes vital for survival. Therapy with glucocorticoids to enhance lung maturity may have immediate and long term consequences for lung structure and function. This series of investigations is directed toward furthering our basic knowledge of lung secretory cell development. We will use structural and biochemical methods to test hypotheses of secretory cell function and to test the probabilities that glucocorticoids damage fetal and newborn lung structure. We intend to study biochemical and 3-dimensional morphologic changes during epithelial cell maturation in the last days of fetal development. We will test hypotheses of the assembly of lamellar bodies and assess the changes in type II cell maturation induced by glucocorticoids. This drug induced accelerated maturation is a relevant clinical concern as the effects are widespread within the lung and have not been shown to be entirely reversible during postnatal growth. A detailed 3-dimensional morphologic study of groups of alveolar septa and of terminal bronchiolar structure will be conducted at allow magnification level that will test the microanatomic basis for theories of cell-cell interactions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032188-08
Application #
3343494
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1984-05-01
Project End
1992-11-30
Budget Start
1991-05-07
Budget End
1992-11-30
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Young, Stephen L; Evans, Katherine; Eu, Jerry P (2002) Nitric oxide modulates branching morphogenesis in fetal rat lung explants. Am J Physiol Lung Cell Mol Physiol 282:L379-85
Savov, J; Wright, J R; Young, S L (2000) Incorporation of biotinylated SP-A into rat lung surfactant layer, type II cells, and clara cells. Am J Physiol Lung Cell Mol Physiol 279:L118-26
Zhao, Y; Young, S L; McIntosh, J C et al. (2000) Ontogeny and localization of TGF-beta type I receptor expression during lung development. Am J Physiol Lung Cell Mol Physiol 278:L1231-9
Herbein, J F; Savov, J; Wright, J R (2000) Binding and uptake of surfactant protein D by freshly isolated rat alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 278:L830-9
Sachs, S; Ghio, A J; Young, S L (1999) Tyloxapol confers durable protection against hyperoxic lung injury in the rat. Exp Lung Res 25:543-59
Zhao, Y; Gilmore, B J; Young, S L (1997) Expression of transforming growth factor-beta receptors during hyperoxia-induced lung injury and repair. Am J Physiol 273:L355-62
Zhao, Y; Young, S L (1996) Requirement of transforming growth factor-beta (TGF-beta) type II receptor for TGF-beta-induced proliferation and growth inhibition. J Biol Chem 271:2369-72
Zhao, Y; Silbajoris, R; Young, S L (1996) Identification and developmental expression of two activin receptors in baboon lung. Biochem Biophys Res Commun 229:50-7
Zhao, Y; Young, S L (1995) Tenascin in rat lung development: in situ localization and cellular sources. Am J Physiol 269:L482-91
Zhao, Y; Young, S L (1995) Expression of transforming growth factor-beta type II receptor in rat lung is regulated during development. Am J Physiol 269:L419-26

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