The long-term objectives of this research are: 1) to study the molecular mechanisms by which surfactant protein gene expression occurs, and 2) to identify and study key regulatory molecules involved in surfactant protein gene expression. Maternal glucocorticoid treatment and Streptozotocin (STZ)-induced maternal diabetes have opposite effects on the expression of fetal surfactant protein A (SP-A). We hypothesize that they will have opposite effects on the regulation of certain nuclear regulatory proteins that represent the common end point for a variety of signals and are involved in the regulation of SP-A gene expression. Based on this hypothesis, these two in vivo rat models will be used as """"""""tools"""""""" to facilitate identification and characterization of nuclear regulatory molecules involved in SP-A gene expression occurs. The specific goals are: 1) To gain further knowledge about the mechanism by which fetal surfactant protein expression is modulated by STZ-induced maternal diabetes; 2) To prepare fetal lung cDNA libraries, which will be screened with the appropriate probes to identify cDNAs whose corresponding mRNA levels are altered by maternal dexamethasone treatment and/or STZ-induced maternal diabetes; 3) To identify the cis-acting elements of the SP-A promoter and trans-acting factors from lung nuclear extracts with which the cis-elements interact to modulate SP-A gene expression. Efforts will be made to determine whether any of the cDNA encoded proteins are identical to trans- acting factors identified from lung nuclear extracts. Knowledge gained about the regulatory molecules involved in SP-A expression and the mechanism(s) by which gene expression takes place can eventually contribute to treatment strategies designed to modify surfactant protein levels and minimize the risk for respiratory distress syndrome under certain conditions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL038288-05
Application #
3354459
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1991-08-15
Project End
1996-01-31
Budget Start
1991-08-15
Budget End
1992-01-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Rayani, H H; Gewolb, I H; Floros, J (1999) Glucose decreases steady state mRNA content of hydrophobic surfactant proteins B and C in fetal rat lung explants. Exp Lung Res 25:69-79
Rayani, H H; Wert Jr, J J; Floros, J (1998) Expression and cDNA sequence of helix destabilizing protein (HDP) in rat lung. Exp Lung Res 24:101-18
Stuempfle, K J; Floros, J (1997) Caution is advised when cDNA expression libraries are screened by southwestern methodologies. Biotechniques 22:260-4
Stuempfle, K J; Koptides, M; Quinn, P G et al. (1996) In vitro analysis of rat surfactant protein A gene expression. Am J Physiol 270:L504-16
Stuempfle, K J; Koptides, M; Karinch, A M et al. (1996) Preparation of transcriptionally active nuclear extracts from mammalian tissues. Biotechniques 21:48-50, 52
Rishi, A K; Joyce-Brady, M; Fisher, J et al. (1995) Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives. Dev Biol 167:294-306
Rayani, H H; Warshaw, J B; Floros, J (1995) Dexamethasone enhances surfactant protein gene expression in streptozotocin-induced immature rat lungs. Pediatr Res 38:870-7
Kouretas, D; Karinch, A M; Rishi, A et al. (1993) Conservation analysis of rat and human SP-A gene identifies 5' flanking sequences of rat SP-A that bind rat lung nuclear proteins. Exp Lung Res 19:485-503
Veletza, S V; Nichols, K V; Gross, I et al. (1992) Surfactant protein C: hormonal control of SP-C mRNA levels in vitro. Am J Physiol 262:L684-7
Guttentag, S H; Phelps, D S; Warshaw, J B et al. (1992) Delayed hydrophobic surfactant protein (SP-B, SP-C) expression in fetuses of streptozotocin-treated rats. Am J Respir Cell Mol Biol 7:190-7

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