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

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 (Δ8-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. Δ8-RAGE mRNA was found in human primary astrocytes and peripheral blood mononuclear cells (PBMCs). Transient transfection experiments demonstrated that Δ8-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.