Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury.
Advanced glycation end products (AGEs) are believed to play an important role in the development of diabetic complications. AGEs are increased in experimental diabetes and treatment with the inhibitor of advanced glycation end products, aminoguanidine, has been shown to attenuate the level of these products in tissues undergoing complications. Recently, an AGE-binding protein has been isolated from bovine lung endothelial 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 diabetes including the kidney, eye, nerve, arteries as well as in a tissue 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 nerve bundles from mesenteric arteries. In the aorta, both AGE and RAGE were found in the intima, media and adventitia. Medial staining was increased in diabetes and was reduced by aminoguanidine treatment. A similar pattern was observed for RAGE in the aorta. In the lung, RAGE was found widely distributed throughout the lung whereas the distribution of AGE staining was more limited, primarily localising to macrophages. The co-localisation of AGEs and RAGE in sites of diabetic microvascular injury suggests that this ligand-receptor interaction may represent an important mechanism in the genesis of diabetic complications.
Soulis
T
T
Department of Medicine, University of Melbourne, Austin, Australia.
Thallas
V
V
Youssef
S
S
Gilbert
R E
RE
McWilliam
B G
BG
Murray-McIntosh
R P
RP
Cooper
M E
ME
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology*; D004198:Disease Susceptibility; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000378:metabolism
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C004479:pimagedine