RAGE (Receptor for Advanced Glycation End products)

Antibody Review

 

 

 

Introduction

  • a member of the immunoglobulin superfamily of cell surface molecules that has multiple ligands and is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. PMID: 16640960, PMID: 16606672, PMID: 16226677

  • has been implicated in the pathogenesis of numerous conditions associated with excessive inflammation. PMID: 16751175

  • a primary transporter of beta-amyloid across the blood-brain barrier (BBB) into the brain from the systemic circulation. PMID: 16865397

  • an important pathogenic factor in the renal changes in an animal model of type 1 diabetes. PMID: 16522729

  • plays a central role in the pathogenesis of diabetic vascular complication. PMID: 16271939, PMID: 12912808

  • a central player in the inflammatory response. PMID: 15488742

Normal Expression

  • RAGE is expressed at low levels in normal tissues, but becomes upregulated at sites where its ligands accumulate. PMID: 15488742

  • In control hippocampus, there was robust RAGE immunoreactivity in neurons, whereas microvascular staining was barely detectable. PMID: 16865397

  • we will describe the AGE-RAGE system, including its localisation in the normal kidney. PMID: 15918107

  • In the present study we demonstrate for the first time that each of the three established RAGE isoforms, as well as three previously unidentified RAGE splicing variants, are normally expressed in the human brain. PMID: 15555779

  • The amount of RAGE in the cerebellum increased with age. RAGE was expressed pre-natally in the external germinal layer and post-natally in the plasma membranes of the granule neurons of the external and internal granule cell layers and in Purkinje cells. PMID: 15341523

  • RAGE is present in the labial salivary glands of both normal and Sjogren's syndrome (SS) patients, with preliminary data suggesting over-expression in SS tissues. PMID: 15228188

  • A monoclonal antibody (MAb) directed against the sequence of human RAGE was reactive against a 35-kDa protein band that was highly expressed in blood cells, plasma proteins, lung, liver, spleen, and brain derived from the immunized mice. PMID: 14501001

  • Pregnancy induced a significant increase in RAGE protein levels in both myometrium and omental vasculature. Blood vessels from women with preeclampsia consistently had intense staining for RAGE in both vessel beds. PMID: 12909002

  • RAGE is abundantly present in the lung. Anti-RAGE immunoreactivity was prominent in alveolar epithelial type I pneumocytes, while it was absent from type II pneumocytes and capillary endothelium. PMID: 9846897

  • receptor for AGEs (RAGE) is such a receptor and is a newly identified member of the immunoglobulin superfamily expressed on endothelial cells (ECs), mononuclear phagocytes (MPs), and vascular smooth muscle cells (SMCs) in both vivo and in vitro. PMID: 8674899

Abnormal Expression

  • In Alzheimer's disease (AD) cases, neuronal RAGE immunoreactivity was significantly decreased. An unexpected finding was the strongly positive microvascular RAGE immunoreactivity. PMID: 16865397

  • Features of autoimmunity have been associated with both Alzheimer's disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. PMID: 16842100

  • Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. PMID: 16815028

  • RAGE-1 and MAGE-9 are expressed in 56% and 38% of Renal cell carcinomas (RCCs). PMID: 15900605  

  • In prostate tissues, untreated prostate cancer tissue and hormone-refractory prostate cancer tissue showed higher RAGE and amphoterin mRNA expression than normal prostate tissue. PMID: 15666359

  • expressed in concordance to the invasion ability of the human biliary cancer cells. PMID: 14571699

  • expression of RAGE (receptor for advanced glycation end products) was found in breast and lung tumor tissues where abundant S100A4 and S100A6 expression was also observed. PMID: 12859967

  • RAGE is expressed in dying neurons and suggest that RAGE may have a role in neuronal cell death mediated by ischemic stress. PMID: 12618340

  • Using brain tissue from AD and nondemented (ND) individuals, RAGE expression was shown to be present on microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal gyrus. PMID: 11520119

Expression Alteration

  • Impaired hepatic function might result in elevated levels of AGEs, as the liver represents the major site of AGE-metabolism. PMID: 16775125

  • Whereas the expressions of AGE-R3 as well as RAGE protein were significantly upregulated in the senescent population, only the upregulation of RAGE is associated with reduced heart function. PMID: 15036400

  • We demonstrate a significantly increased accumulation of AGE and immunoreactivities of RAGE and S100/calgranulins in response to balloon injury in diabetic compared with nondiabetic rats. PMID: 12719284

  • RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. PMID: 10966490

Function

  • There is a growing body of evidence that formation and accumulation of advanced glycation end products (AGEs) progress during normal aging, and at an extremely accelerated rate in diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Furthermore, the interaction by AGEs of their receptor, RAGE, activates down-stream signaling and evokes inflammatory responses in vascular wall cells. PMID: 16712466

  • RAGE as a therapeutic target for treatment of diabetic vascular disease. PMID: 16356122

  • therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes. PMID: 16305050

  • esRAGE is a novel and potential protective factor for the metabolic syndrome and atherosclerosis. PMID: 16224056

  • a new murine model for the study of atherosclerosis in type 2 diabetes and highlight important roles for RAGE in proatherogenic mechanisms in hyperglycemia triggered by insulin resistance. PMID: 16076470

  • In early diabetic retinopathy, the RAGE axis, comprising the cellular receptor and its AGE ligands, is amplified within the retina and is accentuated along the vitreoretinal interface. Antagonism of the RAGE axis in NPDR reduces neurovascular perturbations, providing an important therapeutic target for intervention. PMID: 16043866

  • Nornicotine, AGE, and upregulation of RAGE may be involved in the pathogenesis of periodontal disease associated with smoking. PMID: 16018761

  • RAGE blockade is a novel strategy to promote regeneration in the massively injured liver. PMID: 15699076

  • AGE-RAGE interaction is important in prostate cancer development, and inhibition of this interaction has potential as a new molecular target for cancer therapy or prevention. PMID: 15666359

  • In the diabetic milieu, two classes of RAGE ligands, products of nonenzymatic glycoxidation and S100 proteins, appear to drive receptor-mediated cellular activation and, potentially, acceleration of vascular disease. PMID: 15663911

  • functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta). PMID: 15457210

  • RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction. PMID: 15457210

  • RAGE is a target for drug development to prevent vascular disease in diabetic and nondiabetic subjects. PMID: 15290845

  • RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. PMID: 15155381

  • RAGE is an important pathogenetic factor in the renal changes in an animal model of type 2 diabetes. PMID: 14693711

  • RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. PMID: 12222959

Review Articles

  • RAGE: a multiligand receptor contributing to the cellular response in diabetic vasculopathy and inflammation. PMID: 11129404

  • Atherosclerosis and diabetes: the RAGE connection. PMID: 11122775

  • RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes. PMID: 11042467

  • Enhanced interaction of advanced glycation end products with their cellular receptor RAGE: implications for the pathogenesis of accelerated periodontal disease in diabetes. PMID: 9722686

Applications

 

ELISA

  • By enzyme-linked immunosorbent assay, RAGE and EN-RAGE were detected in the serum. PMID: 16536799

  • we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects. PMID: 16224056

  • ELISA demonstrated a 2.5 times increase of RAGE in AD over control brains. Activated microglia also showed elevated expression of RAGE. PMID: 12671312

Functional Assay (FA)

  • Antibodies against receptor for advanced glycation end products (RAGE) blocked Abeta-induced activation of the p38, JNK pathways, and NF-kappaB in CTL cybrids and offered protection against the neurotoxic effects of Abeta. PMID: 15911356

  • To explore a specific role for RAGE in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine RAGE antibody in db/db mice, a model of obese type 2 diabetes. PMID: 14693711

Immunocytochemistry (ICC))

  • Immunocytochemical analysis by high magnification confocal microscopy showed that RAGE was co-expressed with Amphoterin and SGC in the cell surfaces of granule neurons. PMID: 15341523

  • Immunocytochemical studies demonstrated that in Alzheimer's Disease (AD) the expression of RAGE is elevated in neurons close to neuritic plaque beta-amyloid (Abeta) deposits and in the cells of Abeta containing vessels. PMID: 12671312

Immuno-Electron Microscopy (IEM)

  • This study sought to precisely localise RAGE in the lungs of rat and human by immunohistochemistry, double immunofluorescence and immunoelectron microscopy using a polyclonal antiserum developed against human recombinant RAGE. PMID: 9846897

Immunofluorescence (IF)

  • This observation was supported by immunofluorescence analyses demonstrating that RAGE preferentially localizes at intercellular contact sites, independent of expression of the cytoplasmic domain. PMID: 15539404

Immunohistochemistry (IHC)

  • Immunohistochemical staining of 164 biopsies from patients with varying degree of liver impairment was performed to determine the levels of CML, galectin-3 and RAGE in hepatocytes, Kupffer cells and bile ducts by a semiquantative score. PMID: 16775125

  • Immunohistochemistry and confocal laser scanning microscopy were used to evaluate the expression of RAGE and EN-RAGE in leprosy. PMID: 16536799

  • Immunohistochemistry, real-time RT-PCR, autofluorescence, and ELISA studies were used to localize and quantify the AGE/RAGE axis. PMID: 16043866

  • we performed immunohistochemical studies on the presence of CML-modified proteins, RAGE and activated NF-kappaB in muscle biopsies of patients with polymyositis (PM, n=10), dermatomyositis (DM, n=10), limb girdle muscular dystrophy (LGMD, n=10) and in 10 controls with normal muscle biopsy results. PMID: 15986224

  • We investigated the immunohistochemical expression and immunoblotting of RAGE in labial salivary glands from Sjogren's syndrome (SS) patients. PMID: 15228188

  • We immunohistochemically investigated the occipital lobe of three patients with Creutzfeldt-Jakob disease (CJD) containing with prion protein (PrP) plaques using anti-AGE and RAGE antibodies. PMID: 12057842

  • Immunohistochemistry of gastric carcinoma tissue showed that 62 (65%) of the 96 cases examined were RAGE-positive and that poorly differentiated adenocarcinomas preferentially expressed RAGE protein (38/42, 90%) (p<0.0001). Strong RAGE immunoreactivity was also correlated with depth of invasion and lymph node metastasis (p<0.0001). PMID: 11793367

Western Blotting (WB)

  • Western blot analysis revealed a much higher concentration of RAGE protein in AD hippocampi as compared with controls. PMID: 16865397

  • The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. PMID: 16364297

  • Western blot analysis showed an increased immunoreactivity for CML-modified proteins in PM and DM. In LGMD, CML, RAGE and NF-kappaB were found in regenerating muscle fibers and less frequently in degenerating muscle fibers, and with lower staining intensities than in inflammatory myopathies. PMID: 15986224

  • Western blot and RT-PCR analysis of the AGE receptors from the cardiac auricles in senescent and adult patients was performed and compared with young controls. PMID: 15036400

  • In the present study we examined the possible expression of RAGE by UMR106 and MC3T3E1 osteoblastic cells, by immunoblot analysis. PMID: 12962137

  • The expression of RAGE (receptor for advanced glycation end-products) was examined by Western blot in pancreatic cancer. PMID: 11813576

  • Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. PMID: 11700025