The hypothesis is that delayed lung development in the fetus of the diabetic woman is related to surfactant-associated protein deficiency caused by high levels of insulin.
Aim 1 is to elucidate the signal transduction pathways involved in insulin-mediated inhibition of SP-A and SP-B gene expression. Signal transduction inhibitors, enzyme assays, characterization of signaling intermediates and transfection with dominant negative and constitutively active constructs will be used to test the hypothesis that the PI-3K signal transduction pathway mediates the effects of insulin.
Aim 2 is to identify the cis-acting elements in the SP-A and SP-B genes which mediate the inhibitory effects of insulin. Luciferase reporter gene constructs will be used to localize inhibitory insulin response elements in the 5' flanking region of the human SP-A1 and SP-A2 genes.
Aim 3 is to identify the transcription factors that interact with the SP-A1 and SP-B insulin response elements. Electrophoretic mobility shift assays will be used to test the hypothesis that HNF-3a and C/EBPa mediate the insulin-induced inhibition of SP-A and SP-B gene expression.
Aim 4 is to describe the molecular events (phosphorylation, localization, and/or changes in gene expression) that link signal transduction to transcription factors which interact with the insulin response elements in the SP-A1 and SP-B genes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050050-06
Application #
6498906
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Berberich, Mary Anne
Project Start
1995-09-01
Project End
2005-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
6
Fiscal Year
2002
Total Cost
$220,500
Indirect Cost
Name
University of Iowa
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Oberley, Rebecca E; Goss, Kelli L; Dahmoush, Laila et al. (2005) A role for surfactant protein D in innate immunity of the human prostate. Prostate 65:241-51

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