This renewal of an ongoing and productive Program Project continues to address the response of the lung to injury. The proposed studies have evolved from focusing predominantly on animal models of lung disease to now include many studies utilizing cell culture systems. An earlier strong focus on lung physiology has shifted to the newer experimental approaches of cell and molecular biology. This change represents a natural evolution of the interests and findings of our previous ten years of research and does not reflect a significant alteration in the roster of senior investigators. The proposal is concerned with the general areas of lung matrix, lung cell growth and differentiation and inflammation. It consists of 12 interactive projects and 3 cores. Seven of the projects are direct continuations of ongoing work; three derived from work in the previous period with additional goals and new principal investigators; and two represent new directions related to the central theme of the grant. Projects 1-7 related to elastin, collagen, basement membrane and cytoskeletal synthesis and degradation in cell culture and in vivo, and to the roles that these matrix components play in injury, modulating cell growth, differentiation and gene expression. Projects 7 and 8 deal with animal models of emphysema and chronic airway injury, respectively. Project 9 deals with cell differentiation and mucus secretion in a newly-described dissociated airway-cell culture system. Projects 10-12 deal with activation of lymphocytes, neutrophils and monocyte/macrophages, three important cells involved in lung inflammation. It is anticipated that these studies will provide insights into diseases of lung connective tissue such as pulmonary emphysema and fibrosis, into acute and chronic airway diseases, into lung development and repair, and into the processes of lung inflammation. These studies should also provide important basic information about matrix biology, cell growth and cell differentiation.
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