title: The diverse ligand repertoire of the receptor for advanced glycation endproducts and pathways to the complications of diabetes.
abstract: The multi-ligand receptor RAGE was discovered on account of its ability to bind and transduce the cell stress-provoking signals of advanced glycation endproducts (AGEs). The finding that RAGE also bound pro-inflammatory molecules set the stage for linking RAGE and inflammation to the pathogenesis of diabetic macro- and microvascular complications. In this review, we focus on the roles of RAGE and its ligands in diabetes complications. We recount the findings from mice, rats, swine and human subjects suggesting that RAGE action potently contributes to vascular, inflammatory and end-organ stress and damage in types 1 and 2 diabetes. We detail the efforts to track ligands and RAGE in human subjects with diabetes to address if this axis may be a biomarker reflective of the state of the diabetic complications. Lastly, we suggest specific strategies to tackle AGE-ligand-RAGE interactions as potential therapeutic targets for diabetes and its complications.
authors: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY 10016, United States.
authors: Ravichandran
authors: R
authors: Ramasamy
authors: Shi Fang
authors: SF
authors: Yan
authors: Ann Marie
authors: AM
authors: Schmidt
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000503:physiopathology / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic