Receptor for AGE (RAGE) its Ligands – Cast into Leading Roles in Diabetes the Inflammatory Response

摘要

The actors in the pathogenesis of diabetes and its complications are many and multi-faceted. The effects of elevated levels of glucose are myriad; among these are the generation of Advanced Glycation Endproducts (AGEs), the products of nonenzymatic glycoxidation of proteins and lipids. The finding that AGEs stimulate signal transduction cascades through the multi-ligand receptor RAGE unveiled novel insights into diabetes and its complications. Inextricably woven into AGE-RAGE interactions in diabetes is the engagement of the innate and adaptive immune responses. Although glucose may be the triggering stimulus to draw RAGE into diabetes pathology, consequent cellular stress results in release of pro-inflammatory RAGE ligands S100/calgranulins and HMGB1. We predict that once RAGE is engaged in the diabetic tissue, a vicious cycle of ligand-RAGE perturbation ensues, leading to chronic tissue injury and suppression of repair mechanisms. Targeting RAGE may be a beneficial strategy in diabetes, its complications, and untoward inflammatory responses.