Arg-Gly-Asp (RGD) peptides and peptidomimetics as therapeutics: Relevance for renal diseases

Cells interact with the extracellular matrix and other cells via cell adhes ion receptors which include those of the integrin family. Since the pivotal demonstration in 1984 by Pierschbacher and Ruoslahti that cell adhesion me diated by fibronectin could be inhibited by the simple tripeptide, Arg-Gly- Asp (RGD), then number of other peptide sequences have been shown to recapi tulate integrin-ligand interactions. Similarly, the function of integrins i n 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 susceptib le to modification by integrin antagonists, This possibility has been teste d in experimental acute renal failure with RGD peptides' and in modifying r enal tranpslant rejection in patients by use of antibodies to various leuco cyte or endothelial cell adhesion molecules. The recent development of a nu mber of orally active, non-peptidic integrin antagonists suggests that trea tment of a range of renal diseases may be susceptible to strategies that in volve the blockade of integrin function or modulation of their expression.