AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes.
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.
Miura
Junnosuke
J
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
Uchigata
Yasuko
Y
Yamamoto
Yasuhiko
Y
Takeuchi
Masayoshi
M
Sakurai
Sigeru
S
Watanabe
Takuo
T
Yonekura
Hideto
H
Yamagishi
Sho-Ichi
S
Makita
Zenji
Z
Sato
Akiko
A
Omori
Yasue
Y
Yamamoto
Hiroshi
H
Iwamoto
Yasuhiko
Y
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
D000951:Antigens, Neoplasm; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005985:Glyceraldehyde