Figure 136

Overview of potential therapeutic effects of cyclic integrin-binding peptides. A, During ischemic injury, tubular obstruction occurs as a result of loss of apical membrane, cell contents, and detached cells released into the lumen. B, Also, basolateral integrins diffuse to the apical region of the cell. Biotinylated cyclic peptides containing the sequence cRGDDFV bind to desquamated cells in the ascending limb of the loop of Henle and in proximal tubule cells in ischemic rat kidneys. The desquamated cells can adhere to injured cells or aggregate, causing tubule obstruction.

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FIGURE 13-6 (Continued)

C, When cyclic peptides that contain the RGD canonical binding site of integrins are perfused intra-arterially, the peptides ameliorate the extent of acute renal failure, as demonstrated by a higher glomerular filtration rate (GFR) in rats receiving peptide containing the RGD sequence. B, Proposed mechanism of renal protection by cyclic RGD peptides. By adhering to the RGD binding sites of the integrins located on the apical plasma membrane or distributed randomly on desquamated cells, the cyclic peptide blocks cellular aggregation and tubular obstruction [12-15]. (Courtesy of MS Goligorski, MD.)

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