The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs)

PLoS One. 2014 Jan 27;9(1):e86903. doi: 10.1371/journal.pone.0086903. eCollection 2014.

Abstract

The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and is involved in inflammatory and immune responses. Most importantly, RAGE is considered a receptor for HMGB1 and several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that the Ager gene coding for RAGE first appeared in mammals, and is closely related to other genes coding for cell adhesion molecules (CAMs) such as ALCAM, BCAM and MCAM that appeared earlier during metazoan evolution. RAGE is expressed at very low levels in most cells, but when expressed at high levels, it mediates cell adhesion to extracellular matrix components and to other cells through homophilic interactions. Our results suggest that RAGE evolved from a family of CAMs, and might still act as an adhesion molecule, in particular in the lung where it is highly expressed or under pathological conditions characterized by an increase of its protein levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Adhesion Molecules / genetics*
  • Computational Biology
  • Crystallography, X-Ray
  • Evolution, Molecular
  • Fluorescent Antibody Technique
  • Humans
  • Mammals / genetics*
  • Models, Genetic
  • Models, Molecular*
  • Molecular Sequence Data
  • Phylogeny*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics*
  • Sequence Analysis, DNA
  • Species Specificity
  • Surface Plasmon Resonance

Substances

  • Cell Adhesion Molecules
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic

Grants and funding

This work was supported by grants from the Italian Association for Cancer Research (AIRC, IG-10411) and the Italian Ministry of Health (RF-027B) to MEB, and by Fondazione Monzino and Centro Cardiologico Monzino-IRCCS (RC 2011–2013). GF is supported by a Heisenberg fellowship of the Deutsche Forschungsgemeinschaft (FR 1488/3-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.