Bronchopulmonary dysplasia (BPD) has become the greatest contributor to morbidity in newborn intensive care units. BPD is the clinical consequence of lung injury in the human newborn infant that occurs when functional integrity of the lung is not restored in a timely and orderly manner by the repair process. With a focus on BPD in mind, the goals of this SCOR relate to lung development at the level of cell growth and differentiation, to mechanisms of defense against lung injury, and to repair processes that are initiated in response to lung injury. This SCOR also addresses mechanisms by which clinical interventions can be employed to modify either lung injury or the repair process as a strategy to reduce the incidence and severity of BPD. Finally, in anticipation that the rapidly growing success of lung transplantation will inevitably be extended to the infant with end- stage BPD, this SCOR will attempt to answer questions related to the surfactant system in the transplanted lung, both in regard to performance of the surfactant system in the denervated lung and in regard to the role of surfactant treatment during episodes of rejection. Specific projects in this proposed SCOR involve studies of 1) epidermal growth factor signal transduction in the developing lung, 2) the role of extracellular matrix biosynthesis in fetal rat lung epithelial cell growth and differentiation, 3) the role of pulmonary surfactant associated proteins and related C-type lectins in the lung development, injury and repair, 4) the effects of vitamin A on the regulation of lung epithelial differentiation, 5) the regulation of P450 gene expression and its role in oxidant production by the hyperoxic lung, and 6) the physiologic effects of surfactant treatment in human premature infants. Resources to support these projects are provided by five cores: the Newborn clinical Research Core, the Animal Laboratory Core, the Biomedical Engineering and Informatics Core, the Histopathology and Molecular Biology Core, and the Administrative Core.
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