Related Experiment Video
Updated: Aug 3, 2026
Observing Islet Function and Islet-Immune Cell Interactions in Live Pancreatic Tissue Slices
Published on: April 12, 2021
Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure,
Ai Harashima1, Yasuhiko Yamamoto, Chunmei Cheng
1Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
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.
Insights
Researchers identified a mouse version of esRAGE (endogenous secretory RAGE), a decoy receptor. This discovery aids in understanding RAGE
Area of Science:
- Molecular Biology
- Immunology
- Endocrinology
Background:
- The receptor for advanced glycation end-products (RAGE) is implicated in diabetic vascular complications, neurodegenerative diseases, and inflammation.
- A human splice variant, endogenous secretory RAGE (esRAGE), functions as a decoy receptor for RAGE ligands.
Purpose of the Study:
- To isolate and characterize the murine orthologue of esRAGE.
- To investigate the functional role and expression of murine esRAGE in vivo.
Main Methods:
- Reverse transcription-PCR (RT-PCR) cloning from mouse brain poly(A)+ RNA.
- Transfection experiments to confirm protein translation and function.
- RT-PCR and immunoblotting to detect esRAGE mRNA and protein expression in various tissues.
Main Results:
- A murine esRAGE orthologue was successfully isolated, encoding a 334-amino-acid secretory protein lacking a transmembrane domain.
- Transfection confirmed esRAGE translation and its decoy function in inhibiting AGE-induced NF-kappaB activation.
- esRAGE mRNA and protein were detected in multiple mouse tissues, with increased expression in the kidneys of diabetic mice.
Conclusions:
- The study provides the first animal orthologue of esRAGE.
- Murine esRAGE functions as a secretory decoy receptor, offering a valuable tool for studying its roles in physiological and pathological conditions, including diabetes.
