Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases

Abstract

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.

Protein carbamylation is a hallmark of aging

“…These chemical reactions interfere with normal functions by disrupting molecular conformations, altering enzymatic activities, reducing degradation capacities, or interfering with receptor recognitions (4,36). Among them, glycoxidation has been well-described, and its major contribution to the development of pathophysiological complications of various diseases, such as diabetes mellitus, has been established (37)(38)(39)(40). This reaction had also been shown to participate in the physiological aging process with an accumulation of AGEs in tissues with age.…”

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

“…Full-length RAGE consists of three extracellular immunoglobulin-like domains, a transmembrane domain, and an intracellular domain which is responsible for intracellular signaling (6,7). RAGE interacts with three-dimensional (3D) structures rather than specific amino acid sequences and therefore functions as a multiligand receptor (8).…”

Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation

“…RAGE экспрессируется в клетках эндотелия, гладкомышечных клетках, мононуклеарных фагоцитах, Т и В лимфоцитах, фибробластах, перицитах, нейронах, кардиомиоцитах, гепатоцитах [1,10,11], на более высо-ком уровне -в процессе развития тканей, особенно в центральной нервной системе. В патологических услови-ях, например при сахарном диабете, хроническом воспа-лении или нейродегенеративных заболеваниях, экспрес-сия RAGE значительно возрастает в сосудистых сетях, гемопоэтических компартментах или в ЦНС [12].…”