Arg-Gly-Asp (RGD) Peptides and Peptidomimetics as Therapeutics: Relevance for Renal Diseases

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Abstract
Cells interact with the extracellular matrix and other cells via cell adhesion receptors which include those of the integrin family. Since the pivotal demonstration in 1984 by Pierschbacher and Ruoslahti that cell adhesion mediated by fibronectin could be inhibited by the simple tripeptide, Arg-Gly-Asp (RGD), then number of other peptide sequences have been shown to recapitulate integrin-ligand interactions. Similarly, the function of integrins in normal renal development and physiology and changes in adhesion receptor expression in diseases, such as glomerulonephritis or renal carcinoma, have suggested that abnormal integrin function in the kidney could be susceptible to modification by integrin antagonists. This possibility has been tested in experimental acute renal failure with ‘RGD peptides’ and in modifying renal tranpslant rejection in patients by use of antibodies to various leucocyte or endothelial cell adhesion molecules. The recent development of a number of orally active, non-peptidic integrin antagonists suggests that treatment of a range of renal diseases may be susceptible to strategies that involve the blockade of integrin function or modulation of their expression.