Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression

Abstract

The cell-surface RAGE [receptor for AGE (advanced glycation end-products)] is associated with the development of diabetic vascular complications, neurodegenerative disorders and inflammation. Recently, we isolated a human RAGE splice variant, which can work as a decoy receptor for RAGE ligands, and named it esRAGE (endogenous secretory RAGE). In the present study, we have isolated the murine equivalent of esRAGE from brain polysomal poly(A)+ (polyadenylated) RNA by RT (reverse transcription)-PCR cloning. The mRNA was generated by alternative splicing, and it encoded a 334-amino-acid protein with a signal sequence, but lacking the transmembrane domain. A transfection experiment revealed that the mRNA was actually translated as deduced to yield the secretory protein working as a decoy in AGE-induced NF-kappaB (nuclear factor kappaB) activation. RT-PCR and immunoblotting detected esRAGE mRNA and protein in the brain, lung, kidney and small intestine of wild-type mice, but not of RAGE-null mice. The esRAGE expression was increased in the kidney of diabetic wild-type mice. The present study has thus provided an animal orthologue of esRAGE for clarification of its roles in health and disease.

RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

“…These findings indicate that the role of RAGE in I/R injury is tissue specific. RAGE is a multiligand receptor of the immunoglobulin (Ig) superfamily and is expressed on a wide range of cell types, including renal mesangial cells, (proximal) tubuli, podocytes and Bowman's capsule [3][4][5][6]13] . In line with these results, we showed RAGE expression on podocyte and tubuli but also on cells of the collecting duct.…”

“…The receptor for advanced glycation end products (RAGE) is a multiligand PRR that is expressed in all tissues and on a wide range of cell types, including renal mesangial cells, (proximal) tubuli, podocytes and Bowman's capsule [2][3][4][5][6] and mediates a variety of inflammatory responses in renal diseases [7] . RAGE blockade or deficiency has been shown to suppress hepatic, cardiac, lung and brain I/R-induced injury [8][9][10][11][12] ; however, the contribution of RAGE in renal I/R-induced injury is unknown [13] .…”

RAGE Control of Diabetic Nephropathy in a Mouse Model

“…Direct binding of LMWH to RAGE was assayed by surface plasmon resonance (SPR) assay (Biacore 2000; Biacore, Uppsara, Sweden). Purified secretory isoform of RAGE proteins (16), which have a ligand-binding site, were immobilized on a CM5 research-grade sensor chip according to standard amine coupling procedures (15,25) with an amine coupling kit (Biacore) to a density of ϳ5,500 response units (RU); this density corresponded to 110 fmol/mm 2 . On the control surface, rabbit IgG was immobilized at the same density.…”

Controlling the receptor for advanced glycation end‐products to conquer diabetic vascular complications

“…This is adapted from our original paper 97 . esRAGE, endogenous secretory RAGE; ORF, open reading frame.…”