Comparison of distinct protein isoforms of the receptor for advanced glycation end-products expressed in murine tissues and cell lines

Cell Tissue Res. 2009 Jul;337(1):79-89. doi: 10.1007/s00441-009-0791-0. Epub 2009 May 5.


The receptor for advanced glycation end-products (RAGE) is thought to be expressed ubiquitously as various protein isoforms. Our objective was to use Northern blotting, immunoblotting, and sensitivity to N-glycanase digestion to survey RAGE isoforms expressed in cell lines and mouse tissues in order to obtain a more comprehensive view of the RAGE expressome. Pulmonary RAGE mRNA (1.4 kb) was smaller than cell-line and tissue RAGE mRNA (6 kb-10 kb). Three anti-RAGE antibodies that recognized three distinct RAGE epitopes were used for protein studies (N-16, H-300, and alphaES). Lung expressed three predominant protein isoforms with apparent molecular masses of 45.1, 52.6, and 57.4 kDa (N-16/H-300) and four isoforms at 25.0, 46.9, 52.5, and 54.2 kDa (alphaES). These isoforms were expressed exclusively in lung. Heart, ileum, and kidney expressed a 44.0-kDa isoform (N-16), whereas aorta and pancreas expressed a 53.3-kDa isoform (alphaES). Each of these isoforms were absent in tissue extracts prepared from RAGE(-/-) mice. Cell lines expressed a 70.0-kDa isoform, and a subset expressed a 30.0-kDa isoform (alphaES). Lung RAGE appeared to contain two N-linked glycans. Tissue and cell-line RAGE isoforms were completely insensitive to PNGase F digestion. Thus, numerous RAGE protein isoforms are detectable in tissues and cell lines. Canonical transmembrane and soluble RAGE appear to be expressed solely in lung (N-16/H-300). Non-pulmonary tissues and cell lines, regardless of the source tissue, both express distinct RAGE protein isoforms containing the N-terminal N-16 epitope or the alphaES RAGE epitope encoded by alternate exon 9, but lacking the H-300 epitope.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta / metabolism
  • Cell Line
  • Epitopes / immunology
  • Glycosylation
  • Humans
  • Ileum / metabolism
  • Kidney / metabolism
  • Lung / metabolism
  • Male
  • Mice
  • Myocardium / metabolism
  • Pancreas / metabolism
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*


  • Epitopes
  • Protein Isoforms
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase