title: Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis.
abstract: Many studies have suggested that the expression of RAGE (receptor for advanced glycation end products) is upregulated in human tissues susceptible to the long-term complications of diabetes. From the kidneys to the macrovessels of the aorta, RAGE expression is upregulated in a diverse array of cell types, from glomerular epithelial cells (podocytes) to endothelial cells, vascular smooth muscle cells, and inflammatory mononuclear phagocytes and lymphocytes. Although RAGE was first described as a receptor for advanced glycation end products (AGEs), the key finding that RAGE was also a signaling receptor for proinflammatory S100/calgranulins and amphoterin, led to the premise that even in euglycemia, ligand-RAGE interaction propagated inflammatory mechanisms linked to chronic cellular perturbation and tissue injury. Indeed, such considerations suggested that RAGE might even participate in the pathogenesis of type 1 diabetes. Our studies have shown that pharmacological and/or genetic deletion/mutation of the receptor attenuates the development of hyperglycemia in NOD mice; in mice with myriad complications of diabetes, interruption of ligand-RAGE interaction prevents or delays the chronic complications of the disease in both macro- and microvessel structures. Taken together, these findings suggest that RAGE is "at the right place and time" to contribute to the pathogenesis of diabetes and it complications. Studies are in progress to test the premise that antagonism of this interaction is a logical strategy for the prevention and treatment of diabetes.
authors.affiliation: Division of Surgical Science, Department of Surgery, Columbia University Medical Center, 630 West 168th St., P&S 17-501, New York, New York 10032, USA.
authors.forename: William
authors.initials: W
authors.lastname: Kim
authors.forename: Barry I
authors.initials: BI
authors.lastname: Hudson
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Guo
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Rong
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Wu
authors.initials: W
authors.lastname: Qu
authors.forename: Evanthia
authors.initials: E
authors.lastname: Lalla
authors.forename: Shulamit
authors.initials: S
authors.lastname: Lerner
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: Shirley Shi Du
authors.initials: SS
authors.lastname: Yan
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Kevan
authors.initials: K
authors.lastname: Herold
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001158:Arteries / Q000293:injuries / Q000473:pathology; D001161:Arteriosclerosis / Q000503:physiopathology; D048909:Diabetes Complications / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D014652:Vascular Diseases / Q000503:physiopathology
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic