title: 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 (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.
authors.affiliation: Department of Microbiology, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong Seodaemoon-gu, Seoul 120-752, South Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Park
authors.forename: Soo In
authors.initials: SI
authors.lastname: Yeon
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Youn
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sasaki
authors.forename: In-Hong
authors.initials: IH
authors.lastname: Choi
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D018388:Codon, Terminator; D005091:Exons; D016368:Frameshift Mutation; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018388:Codon, Terminator; D017127:Glycation End Products, Advanced; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D011994:Recombinant Proteins