title: AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes.
abstract: Advanced glycation end product (AGE) engagement of a cell surface receptor for AGE (RAGE) has been implicated in the development of diabetic complications. In this study, we determined the RAGE mRNA levels in monocytes from type 1 diabetic patients and analyzed their relationship with diabetic vascular complications. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the monocyte expression of RAGE mRNA was significantly lower in patients with retinopathy than in those without retinopathy and was also significantly down-regulated in patients with nephropathy in comparison with those without nephropathy. Experiments with monocyte-enriched cultures revealed that RAGE mRNA and protein levels were down-regulated by the exposure to glyceraldehyde-derived AGE-the recently identified high-affinity RAGE ligand. Accordingly, we then assayed for the serum levels of glyceraldehyde-derived AGE as well as those of carboxymethyllysine (CML)-the known RAGE ligand and related them to the monocyte levels of RAGE mRNA. This screen revealed a negative correlation between the two parameters. The results thus suggest that the decrease in monocyte RAGE expression can be at least partly accounted for by the ligand engagement and may be a factor contributing to the development of diabetic vascular complications.
authors.affiliation: Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. jmiurara@dmc.twmu.ac.jp
authors.forename: Junnosuke
authors.initials: J
authors.lastname: Miura
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Uchigata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Sigeru
authors.initials: S
authors.lastname: Sakurai
authors.forename: Takuo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideto
authors.initials: H
authors.lastname: Yonekura
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Zenji
authors.initials: Z
authors.lastname: Makita
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Yasue
authors.initials: Y
authors.lastname: Omori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000951:Antigens, Neoplasm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000097:blood*; D005985:Glyceraldehyde / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005985:Glyceraldehyde