Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a possible mechanism of pericyte loss in diabetic microangiopathy.
The influence of advanced glycosylation end products (AGE) on bovine retinal pericytes was investigated. When pericytes were cultured with AGE-bovine serum albumin (BSA), pericyte growth was significantly retarded in a dose-dependent manner. They also exhibited an immediate toxicity to pericytes. However, MRC-5 human fibroblasts were totally resistant to AGE-BSA. Moreover, antisense oligonucleotides complementary to mRNA coding for AGE receptor were found to reverse the AGE-induced decrease in viable pericyte number, although the mRNA level was about one order of magnitude lower in pericytes than in the fibroblasts. These results indicate that pericytes may possess a peculiar sensitivity to AGE, and that AGE ligand-receptor interactions may play an important role in the pathogenesis of pericyte loss, the principal change in diabetic microangiopathies.
Yamagishi
S
S
Department of Biochemistry, Kanazawa University School of Medicine, Japan.
Hsu
C C
CC
Taniguchi
M
M
Harada
S
S
Yamamoto
Y
Y
Ohsawa
K
K
Kobayashi
K
K
Yamamoto
H
H
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000187:drug effects*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012710:Serum Albumin, Bovine