The AGE-receptor in the pathogenesis of diabetic complications.
Native glucose-derived glycation derivatives (advanced glycation end products, AGE) in vascular, renal and neuronal tissues contribute to organ damage. Glycation derivatives include a number of chemically and cell-reactive substances, also termed glycoxidation products or glycotoxins (GT). Cell-associated AGE-specific receptors (AGE-Rs), AGE-R1-3, RAGE, as well as the scavenger receptors ScR-II and CD-36 that are present on vascular, renal, hemopoietic, and neuronal/glial cells, serve in the regulation of AGE uptake and removal. AGE-Rs also modulate cell activation, growth-related mediators, and cell proliferation, consequently influencing organ structure/function. This occurs via oxidant stress triggered via receptor-dependent or -independent pathways, and leads to signal activation pathways, resulting in pro-inflammatory responses. In susceptible individuals, the AGE-R expression/function may be subject to environmental or gene-related modulation, which in turn may influence tissue-specific gene functions. In this context, altered expression and activity of AGE-R components has recently been found in both mouse diabetes models and humans with diabetic complications. Although several gene polymorphisms are detected in most AGE-R components, no significant correlation to diabetic complications has as yet been found. Further investigation is underway to define whether primary or secondary genetic links of pathogenic significance exist in this system. Various AGE-binding peptides or soluble receptors have emerged as potential sequestering agents for toxic AGEs as potential therapies for diabetic complications.
Vlassara
H
H
Mount Sinai School of Medicine, New York, NY 10029, USA. helen.vlassara@mssm.edu
D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress
D017127:Glycation End Products, Advanced