The research proposed in this application will examine heparan sulfate proteoglycan and how it is changed in various disorders of increased glomerular permeability. These studies will characterize the heparan sulfate in some detail going beyond mere histologic examination of changes in glomerular anionic sites. Changes in heparan sulfate are not just a matter of being increased or decreased, but there are probably very subtle structural and sulfate content changes occurring in this molecule in these disorders. Second, these studies will examine whether glycosaminoglycans can play any role in the formation of immune deposits by binding cationic antigens, antibodies or immune complexes. Lastly, there is the question of what is mediating the changes in heparan sulfate that have been identified in some of the preliminary studies presented here. These studies will attempt to determine whether complement may be one such mediator of changes in glomerular heparan sulfate proteoglycan.
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