Related Experiment Video
Updated: Nov 30, 2025
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate
James N Tsoporis1, Erifili Hatziagelaki2, Sahil Gupta1,3
1Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1T8, Canada.
Abstract:
We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.
Insights
Lower soluble RAGE (sRAGE) levels in middle-aged type 2 diabetes (T2D) patients may increase vascular remodeling risk. Reduced sRAGE limits trapping of pro-inflammatory RAGE ligands, AGEs and S100B, contributing to diabetic complications.
Area of Science:
- Endocrinology
- Vascular Biology
- Molecular Medicine
Background:
- The receptor for advanced glycation end products (RAGE) pathway is implicated in vascular complications.
- Soluble RAGE (sRAGE) acts as a decoy receptor, potentially mitigating RAGE signaling.
- Age and type 2 diabetes (T2D) influence RAGE pathway components and vascular health.
Purpose of the Study:
- To investigate the association between plasma sRAGE and RAGE ligand levels and vascular remodeling in healthy individuals and T2D patients.
- To determine the impact of age and glucose tolerance status (NGT, IGT, T2D) on these markers.
- To assess the in vitro effects of RAGE ligands and sRAGE on vascular smooth muscle cells.
Main Methods:
- Plasma concentrations of sRAGE, RAGE ligands (AGEs, S100B, S100A1, S100A6), and Fas ligand were measured using ELISA in stratified age and glucose tolerance groups.
- Adult rat aortic smooth muscle cells (ASMC) were cultured to evaluate the apoptotic and inflammatory potential of RAGE ligands and sRAGE.
- Statistical analysis compared marker levels across different groups and assessed in vitro responses.
Main Results:
- Aging in normal glucose tolerant (NGT) individuals increased AGEs and S100B while decreasing sRAGE, S100A1, and S100A6.
- Middle-aged T2D patients exhibited higher S100B, AGEs, and FasL, and lower sRAGE, S100A1, and S100A6 compared to NGT and impaired glucose tolerance (IGT) groups.
- In vitro, AGEs and S100B induced inflammation and apoptosis in ASMC, effects attenuated by sRAGE.
Conclusions:
- Lower circulating sRAGE levels in middle-aged T2D patients may impair the clearance of pro-apoptotic and pro-inflammatory RAGE ligands (AGEs, S100B).
- This impaired clearance could contribute to vascular remodeling and increase the risk of diabetic vascular complications.
- Targeting the RAGE pathway and modulating sRAGE levels may offer therapeutic strategies for T2D vascular complications.
Related Concept Videos
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:28Insulin: The Receptor and Signaling Pathways
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:09GPCRs Regulate Adenylyl Cylase Activity
01:16Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
01:15G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...