SURFACTANT PROTEIN REGULATION IN DEVELOPING LUNG

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Pulmonary surfactant serves the primary function of lowering surface tension at the air-liquid interface in the lung, thereby preventing alveolar collapse at low lung volumes. Deficiency in surfactant production has been incontrovertibly linked to respiratory distress syndrome (RDS) in the neonate. Surfactant is a complex combination of phospholipids, cholesterol, and three families of lung-specific surfactant proteins. The surfactant protein found in greatest abundance is a glycoprotein of with a reduced MW of 26-38 KDa that has been designated SP-A. The two remaining surfactant proteins are very hydrophobic. These two proteins have MWs of 18 KDa and 5-8 kDa, and have been designated SP-B and SP-C, respectively. While the full range of functions of the surfactant proteins are not known precisely, it has been demonstrated that all three affect the surface tension-lowering properties of surfactant phospholipids. Since RDS is a condition caused by surfactant deficiency, understanding the factors that regulate expression of these proteins of surfactant in clearly important. The intent of this proposal is to determine the factors affect initiation of expression of the three surfactant proteins in the predifferentiated lung, along with the factors that cause acceleration of expression can be divided into three general groups: hormones and other soluble factors, epithelial cell-extracellular matrix interactions, and epithelial- mesenchymal interactions. We will evaluate response of fetal lung cells to these factors by several methods. These will include quantitation of content of the surfactant proteins and their mRNAsl, measurement of surfactant protein synthesis, determination of relative rates of specific surfactant proteins. The overall goal of this project is to determine which endocrine and paracrine influences regulate expression of SP-A, SP-B, and SP-C in the developing lung. Knowledge of how the surfactant proteins are regulated may result in new approaches for the prevention and treatment of RDS.