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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory and Applied Physiology Study Section (RAP)
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Pennsylvania State University
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