The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes

Abstract

The soluble receptor for advanced glycation end-products (sRAGE) has been classically considered a sink for pro-inflammatory RAGE ligands and as such has been associated with protection from inflammatory stress and disease. An alternative, though not mutually exclusive view is that high levels of sRAGE in circulation reflect the overstimulation of cell surface RAGE which if persistent, lead to the amplification of pro-inflammatory processes and the exacerbation of pathological states. With these two scenarios in mind this review focuses on the potential role of sRAGE as a prospective biomarker of disease risk and adverse outcomes.

AGEs-related dysfunctions in PCOS: evidence from animal and clinical research

“…AGEs, in turn, activate proinflammatory pathways and reactive oxygen species (ROS) generation (Fleming et al 2011, Papachristoforou et al 2020. This effect is mediated by engagement of specific cell-surface receptors, such as the receptor for AGEs (RAGE), a multiligand member of the immunoglobulin superfamily of cell surface (Erusalimsky et al 2021). AGE-RAGE interaction activates intracellular multiple inflammatory signaling pathways including the transcription factor nuclear factor KB (NFKB) and its target genes, TNFa, interleukin1, interleukin 6, and VCAM1 (Fig.…”

“…AGEbound RAGE triggers the activity of NADPH oxidase increasing the production of ROS. Two RAGE isoforms are present that are known as soluble RAGEs (sRAGEs): the cleaved form, known as cRAGE, is generated by proteolytic cleavage of membrane-bound RAGE by the metalloproteases ADAM-10 and MMP-9; the second form of sRAGE, called esRAGE (endogenous secretory RAGE) that results from alternative splicing of RAGE pre-mRNA (Erusalimsky et al 2021). The expression of esRAGE may be influenced by impaired glucose metabolism.…”

Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study

“…These results seem conflicting, especially when reckoning with the role of sRAGE as a decoy receptor for membrane-bound RAGE, which binds RAGE ligands but does not initiate the AGE/RAGE axis and hence neutralizes the deleterious impacts [ 32 ]. Nevertheless, an innovative view argued that sRAGE levels may not be sufficient enough to antagonize RAGE-ligand interactions in light of the inflammatory situations where RAGE itself is also upregulated [ 33 ]. On the other hand, the elevated sRAGE level may be attributed to the overstimulation of cell surface RAGE by inflammatory signals, and thus increases the ectodomain shedding into circulation [ 34 ].…”

“…On the other hand, the elevated sRAGE level may be attributed to the overstimulation of cell surface RAGE by inflammatory signals, and thus increases the ectodomain shedding into circulation [ 34 ]. Some scientists therefore embrace the viewpoint that sRAGE is a prospective biomarker of disease but the clinical applications should be distinguished depending on different scenarios [ 2 , 33 ]. Findings in the present study proposed that sRAGE may incline to a be a predictor of risk in sarcopenia.…”

Special issue on ‘Biomarkers of Oxidative Stress, Aging and Nutrition in Human Studies’

“…Recent glyco-redox studies and novel therapeutic approaches for the treatment of related diseases are discussed in the review by Khoder-Agha et al [ 5 ]. Erusalimsky focuses on the use of soluble Receptor for Advanced Glycation-End Products (sRAGE) as a biomarker of disease risk and adverse outcomes [ 6 ]. His conclusions why sRAGE may reflect chronic inflammation and multimorbidity rather than a healthy state and thus sRAGE is a promising biomarker of disease risk and adverse outcomes are detailed in this review [ 6 ].…”