ADVANCED GLYCATION END-PRODUCTS AND THEIR RECEPTORS CO-LOCALIZE IN RAT ORGANS SUSCEPTIBLE TO DIABETIC MICROVASCULAR INJURY

Advanced glycation end products (AGEs) are believed to play an importa nt role in the development of diabetic complications. AGEs are increas ed in experimental diabetes and treatment with the inhibitor of advanc ed glycation end products, aminoguanidine, has been shown to attenuate the level of these products in tissues undergoing complications. Rece ntly, an AGE-binding protein has been isolated from bovine lung endoth elial cells and termed the receptor for advanced glycated end products (RAGE). The present study sought to determine the distribution of AGE and RAGE in tissues susceptible to the long-term complications of dia betes including the kidney, eye, nerve, arteries as well as in a tissu e resistant to such complications, the lung. Using polyclonal antisera both AGE and RAGE were found to co-localize in the renal glomerulus. AGE staining was clearly increased with age and was further increased by diabetes. Aminoguanidine treatment reduced AGE accumulation in the kidney. Co-localisation of AGE and RAGE was demonstrated in the inner plexiform layer and the inner limiting membrane of the retina and in n erve bundles from mesenteric arteries. In the aorta, both AGE and RAGE were found in the intima, media and adventitia. Medial staining was i ncreased in diabetes and was reduced by aminoguanidine treatment. A si milar pattern was observed for RAGE in the aorta. In the lung, RAGE wa s found widely distributed throughout the lung whereas the distributio n of AGE staining was more limited, primarily localising to macrophage s. The co-localisation of AGEs and RAGE in sites of diabetic microvasc ular injury suggests that this ligand-receptor interaction may represe nt an important mechanism in the genesis of diabetic complications.