Targeting RAGE Signaling in Inflammatory Disease

Barry Hudson, Marc E Lippman

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including bacterial endotoxin, respiratory viruses, and microbial DNA. RAGE is expressed at low levels under normal physiology, but it is highly upregulated under chronic inflammation because of the accumulation of various RAGE ligands. Blocking RAGE signaling in cell and animal models has revealed that targeting RAGE impairs inflammation and progression of diabetic vascular complications, cardiovascular disease (CVD), and cancer progression and metastasis. The clinical relevance of RAGE in inflammatory disease is being demonstrated in emerging clinical trials of novel small-molecule RAGE inhibitors.

Original languageEnglish (US)
Pages (from-to)349-364
Number of pages16
JournalAnnual Review of Medicine
Volume69
DOIs
StatePublished - Jan 29 2018

Keywords

  • Cancer
  • Cardiovascular disease
  • Diabetes
  • HMGB1
  • Inflammation
  • Pattern recognition receptors
  • Receptor for advanced glycation end-products
  • S100 proteins
  • Small-molecule inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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