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Assessment of Kidney Function in Mouse Models of Glomerular Disease
09:16

Assessment of Kidney Function in Mouse Models of Glomerular Disease

Published on: June 30, 2018

Receptor for advanced glycation end products is a promising target of diabetic nephropathy

Yasuhiko Yamamoto1, Toshio Doi, Ichiro Kato

  • 1Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. yamamoto@med.kanazawa-u.ac.jp

Annals of the New York Academy of Sciences
|July 23, 2005
PubMed

Insights

Advanced glycation end products (AGEs) interacting with the receptor for AGE (RAGE) worsen diabetic kidney disease. Inhibiting AGEs or RAGE, and a soluble form called esRAGE, show promise for treating these vascular complications.

Area of Science:

  • Biomedical Science
  • Vascular Biology
  • Diabetology

Background:

  • Advanced glycation end products (AGEs) and receptor for AGE (RAGE) interactions are linked to diabetic vascular complications, impacting quality of life and longevity.
  • Diabetic nephropathy is a significant complication leading to disability and reduced life expectancy.

Purpose of the Study:

  • To investigate the role of RAGE in diabetic nephropathy.
  • To identify and characterize a novel soluble form of RAGE as a potential therapeutic target.

Main Methods:

  • Utilized RAGE-overexpressing and RAGE-deficient transgenic mice models.
  • Analyzed vascular polysomal poly(A)+ RNA to identify splice variants.
  • Assessed the protective effects of soluble RAGE (esRAGE) against AGE-induced vascular cell injury.

Main Results:

  • Diabetes-induced RAGE overexpression exacerbated nephropathy indices in mice.
  • RAGE deficiency markedly ameliorated diabetic nephropathy.
  • Identified a novel splice variant, endogenous secretory RAGE (esRAGE), a soluble decoy receptor detected in human circulation.
  • esRAGE demonstrated protection against AGE-induced vascular cell injuries.

Conclusions:

  • RAGE plays a critical role in the pathogenesis of diabetic vascular complications, particularly nephropathy.
  • RAGE is a promising therapeutic target for managing diabetic vascular disease.
  • Endogenous secretory RAGE (esRAGE) may contribute to individual resistance against diabetic vascular complications.

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