title: The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification.
abstract: AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication.
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: Amber M
authors.identifier: 0000-0002-0423-6526
authors.initials: AM
authors.lastname: Kay
authors.affiliation: Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: C LaShan
authors.identifier: 0000-0002-2908-7977
authors.initials: CL
authors.lastname: Simpson
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: James A
authors.identifier: 0000-0001-6024-6297
authors.initials: JA
authors.lastname: Stewart
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism*; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; C000606290:SOD1 protein, human; D016212:Transforming Growth Factor beta; D060749:alpha-2-HS-Glycoprotein; D000072105:Superoxide Dismutase-1; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases