STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

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DESCRIPTION: (Adapted from the applicant's abstract) - This is a revised application for a renewal of a grant to study structural determinants of glomerular permeability. The glomerulus is a complex filter with remarkably high hydraulic conductivity and low macromolecular permeability. Although abnormalities of each of these functions accompany renal disease, the mechanisms by which the filtration barrier is maintained and regulated are not well understood. The investigator proposes to test two central hypotheses: 1. Glomerular permeability is maintained and modulated by cells of the filtration barrier; 2. functional alterations in glomerular epithelial cells can perpetuate or augment abnormalities of the glomerular permeability barrier. Experimental questions address 1) the mechanisms by which hydraulic and macromolecular permeability of the glomerulus is maintained and regulated; the effects of hormones such as ANG II and IGF-1 on permeability, the effects of alterations in cytoskeleton on glomerular permeability and the role of the cytoskeleton in hormones in mediating permeability changes and 2) the role of abnormalities in macromolecular permeability in causing alterations of glomerular epithelial cell function, the effects of albumin exposure on glomerular permeability, and the mechanisms of cellular albumin uptake and oxidant production after exposure to albumin.