This revised application seeks continued support for a broad program in renal research directed at understanding the cellular and molecular mechanisms of renal disease. The investigators will study the cellular and molecular pathobiology of the kidney including endothelial cell differentiation of renal microvasculature, the regulation of cytoskeletal organization and polarity of membrane proteins in renal epithelial cells in vivo, the definition of the molecular architecture and assembly of the renal brush border. These problems will be addressed primarily in renal cell culture systems, including primary and early passage cultures of endothelial cells, renal epithelial cells, and in established cell lines such as the MDCK, and LLCPK, cells. In addition, the phenotype of specific functional defects in the renal epithelial cell cytoskeleton or it's cell adhesion properties will be examined in transgenic mice. Morphological, biochemical, immunochemical, cell biological and molecular biological techniques will be used to investigate these problems. core facilities including a central imaging core will support the group research effort, and serve as a focus for a wide range of collaborative studies. The research projects are directed at an evaluation of the fundamental properties of renal cells and matrix and the role that these components may plan int he altered structure and function associated with various forms of renal disease and thus provide a base of knowledge for a rational approach to prevention and treatment.
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