Soluble RAGE: therapy and biomarker in unraveling the RAGE axis in chronic disease and aging.
The multi-ligand Receptor for Advanced Glycation Endproducts (RAGE) is implicated in the pathogenesis and progression of chronic diseases such as diabetes and immune/inflammatory disorders. Recent studies are uncovering the precise mechanisms by which distinct RAGE ligands bind the extracellular (soluble) domain of the receptor at the V-, C1- and/or C2-immunoglobulin like domains. Experiments using soluble RAGE in animals as a ligand decoy have illustrated largely beneficial effects in reducing vascular and inflammatory stress and, thereby, preventing long-term tissue damage in models of diabetes and immune/inflammatory disorders. Measurement of soluble RAGE levels in the human, both "total" soluble RAGE and a splice variant-derived product known as endogenous secretory or esRAGE, holds promise for the identification of potential therapeutic targets and/or biomarkers of RAGE activity in disease. In this article, we review the evidence from the rodent to the human implicating RAGE in the diverse disease states in which its ligands accumulate.
Yan
Shi Fang
SF
Department of Surgery, Columbia University, New York, NY 10032, United States.
Ramasamy
Ravichandran
R
Schmidt
Ann Marie
AM
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic