This proposal is directed toward improving our understanding of factors associated with neonatal lung injury and its long term clinical consequences. The component projects will examine the basis of acute lung injury as well as the sequence of injury that result in long term structural and functional alterations of the airway. The Center will include 6 major projects in addition to defined cores for administrative and programmatic needs of the Center. Specific projects are: 1) Neonatal Lung Matrix Drives Lung Repair. This study will define the influence of oxidant injury on lung epithelial basement membrane matrix interactions; 2) Alveolar Epithelial Differentiation in Oxidant Injury. This study will examine the influence of oxidant injury on Na+/K+ ATPase and gammaglutamyltransferase in lung; 3) Relationship Between Stress Proteins and Antioxidants in Hyperoxia. The heat shock response has been shown to be important in a variety of systems involved in injury and repair. We will examine heat shock proteins in relationship to endogenous antioxidant mechanisms following hyperoxic insult; 4) Regulation of Surfactant Phospholipid Metabolism in Injured Adult and Developing Lungs. This project will examine surfactant phospholipid synthesis in different populations of type II cells following silica induced lung injury; 5) The Influence of Butyrate Acid on SP-A Gene Transcription. This project will study the response of lung to a specific biochemical insult associated with alterations in gene expression; 6) Energetics of Breathing in Infants with Chronic Lung Disease. In this project, we will study alterations in lung work, respiratory efficiency and energy expenditure in infants with BPD who represent the final common pathway of acute lung injury. The SCOR will include 2 Cores which will provide support for the programmatic, educational, and oversight components as well as biostatistical support and a shared instrument facility. A shared morphology and electron microscopy core will provide support for the component laboratory projects. The interactions and shared knowledge provided through the Center will lead to a better understanding of the events underlying lung injury that will be essential before rational strategies for prevention can be rigorously developed and tested.
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