Receptor for Advanced Glycation Endproducts (RAGE), Its Ligands, and Soluble RAGE: Potential Biomarkers for Diagnosis and Therapeutic Targets for Human Renal Diseases

AbstractAdvanced glycation endproducts (AGE) are a group of complex and heterogeneous molecules, sharing some common characteristics such as covalent cross-link formation among proteins, the effect of transforming the colour of food products into yellow-brown colours and fluorescence formation. AGE are linked to many diseases including diabetes, renal diseases, CVD, liver diseases, neuro-degenerative and eye disorders, female reproductive dysfunction, and even cancer. AGE are formed endogenously but are also provided from exogenous sources including diet and tobacco. Western diet, rich in processed and/or heat-treated foods, fat and sugar, increases the exposure to AGE. The foods that contain high levels of fat and protein are generally rich in terms of AGE, and are also prone to AGE formation during cooking compared with carbohydrate-rich foods such as vegetables, fruits, legumes and whole grains. The present article aimed to review the literature about the effects of different cooking methods and conditions on the AGE content of food and AGE formation mechanisms using a comprehensive approach.

Download Full-text

Soluble Receptor for Advanced Glycation Endproducts Is Decreased in Patients with Juvenile Idiopathic Arthritis (ERA Category) and Inversely Correlates with Disease Activity and S100A12 Levels

The Journal of Rheumatology ◽

10.3899/jrheum.110058 ◽

2011 ◽

Vol 38 (9) ◽

pp. 1994-1999 ◽

Cited By ~ 20

Author(s):

ARPITA MYLES ◽

VISHAD VISWANATH ◽

YOGESH PREET SINGH ◽

AMITA AGGARWAL

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Advanced Glycation Endproducts ◽

Tender Joint Count ◽

Healthy Controls ◽

Advanced Glycation ◽

Tender Joint ◽

Glycation Endproducts ◽

Paired Samples ◽

Soluble Rage

Objective.Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category].Methods.sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range).Results.The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64–1887) vs 1542 (627–3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51–799) vs 481 (134–1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573–1415) than serum (638; 208–779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p < 0.01.), ESR (r = −0.306; p < 0.01), and SJC (r = −0.237; p < 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease.Conclusion.Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.

Download Full-text

Effekte von nutritiven Advanced Glycation Endproducts (AGE) auf Plasmaspiegel von sCD40L bei Patienten mit Diabetes mellitus – Effekte von Benfotiamin

Diabetologie und Stoffwechsel ◽

10.1055/s-2006-943867 ◽

2006 ◽

Vol 1 (S 1) ◽

Author(s):

B Stratmann ◽

T Gawlowski ◽

A Stirban ◽

M Negrean ◽

Y Mattern ◽

...

Keyword(s):

Diabetes Mellitus ◽

Advanced Glycation Endproducts ◽

Advanced Glycation ◽

Glycation Endproducts

Download Full-text

Comment on “Advanced glycation endproducts in food and their effects on health” by Poulsen et al. (2013) Food and Chemical Toxicology 60, 10–37

Food and Chemical Toxicology ◽

10.1016/j.fct.2013.12.001 ◽

2014 ◽

Vol 64 ◽

pp. 411 ◽

Cited By ~ 2

Author(s):

Alin Stirban ◽

Diethelm Tschoepe

Keyword(s):

Advanced Glycation Endproducts ◽

Advanced Glycation ◽

Glycation Endproducts ◽

Chemical Toxicology

Download Full-text

The Immune Tolerance Role of the HMGB1-RAGE Axis

Cells ◽

10.3390/cells10030564 ◽

2021 ◽

Vol 10 (3) ◽

pp. 564

Author(s):

Haruki Watanabe ◽

Myoungsun Son

Keyword(s):

Immune Responses ◽

Immune Tolerance ◽

Lupus Erythematosus ◽

Advanced Glycation Endproducts ◽

High Mobility ◽

Chromatin Binding ◽

Advanced Glycation ◽

Glycation Endproducts ◽

Extracellular Milieu

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.

Download Full-text