The investigators hypothesize that the cellular responses to local and distant production of TGF-b are set by the expression of specific receptors for the cytokine.
Aim 1 is to determine the temporal and spatial expression of rat lung TGFR during ontogeny.
Aim 2 is to correlate the expression of rat lung TGFR during development with their expression during the repair of perinatal lung injury.
Aim 3 is to test whether TGFRI or TGFRII controls production of ECM components by expressing mutated TGFRI and TGFRII in fibroblasts cultured from lungs of fetal rats.
Aim 4 is to test the role of fibroblast TGFR expression as instruction for lung development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032188-14
Application #
6017219
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1984-05-01
Project End
2001-11-30
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
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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