Enhanced expression of platelet-derived growth factor-beta receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy.
Coronary heart disease is a major complication of diabetic subjects, and platelet-derived growth factor (PDGF) has been implicated in the development of atherosclerosis. We investigated the effects of high glucose on expression of PDGF-beta receptor. In a binding assay with 125I-labeled PDGF-BB homodimer, high concentrations of glucose increased high-affinity binding of PDGF-BB on human monocyte-derived macrophages and rabbit aortic medial smooth muscle cells. Northern blot analysis confirmed the enhanced effect of glucose on expression of PDGF-beta receptor mRNA in human monocyte-derived macrophages. The protein kinase C inhibitor, staurosporin, completely suppressed an increase in PDGF-BB binding by high glucose, and high glucose significantly activated protein kinase C. These results indicated that PDGF-beta receptor expression was enhanced by high glucose through the activation of protein kinase C. Furthermore, we observed similar effects of high glucose on both PDGF-beta receptor expression and protein kinase C activation in rat mesangial cells and human capillary endothelial cells. Our results suggest that stimulation of the PDGF system is significantly involved in the development not only of diabetic atherosclerosis but also of microangiopathy.
Inaba
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ishibashi
S
S
Gotoda
T
T
Kawamura
M
M
Morino
N
N
Nojima
Y
Y
Kawakami
M
M
Yazaki
Y
Y
Yamada
N
N
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D015152:Blotting, Northern; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D019311:Staurosporine; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism*
D000470:Alkaloids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C; D019311:Staurosporine; D005947:Glucose