Expression of a novel secreted splice variant of the receptor for advanced glycation end products (RAGE) in human brain astrocytes and peripheral blood mononuclear cells

Mol Immunol. 2004 Mar;40(16):1203-11. doi: 10.1016/j.molimm.2003.11.027.

Abstract

The engagement of the receptor for advanced glycation end products (RAGE) on the cell surface induces cellular dysfunction in a number of pathophysiological situations of vascular dysfunction, tumor cell invasion, inflammatory response, and T cell infiltration. The administration of truncated, soluble RAGE can modulate RAGE-mediated perturbations. Here, we report a novel splice variant (delta8-RAGE) of RAGE mRNA, which lacks exon 8 of the genomic RAGE gene and contains an early stop codon in exon 10 due to a frame shift mutation. delta8-RAGE mRNA was found in human primary astrocytes and peripheral blood mononuclear cells (PBMCs). Transient transfection experiments demonstrated that delta8-RAGE mRNA was translated into a secretory protein as deduced. Moreover, two different segments of the spliced variant were identified in PBMCs by RT-PCR. The findings of this study suggest that the diverse splicing variants of RAGE are possible in many tissues and their products may influence the RAGE-mediated pathogenesis and immune modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Astrocytes / metabolism*
  • Brain / cytology
  • Codon, Terminator
  • Exons
  • Frameshift Mutation
  • Gene Expression
  • Glycation End Products, Advanced / chemistry
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Codon, Terminator
  • Glycation End Products, Advanced
  • Protein Isoforms
  • Receptors, Immunologic
  • Recombinant Proteins