Role of PKC and TGF-beta receptor in glucose-induced proliferation of smooth muscle cells.
The role of protein kinase C (PKC) and transforming growth factor (TGF)-beta in the proliferation of vascular smooth muscle cells (SMCs) under a high glucose condition was investigated. [3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531. The amount of active and total TGF-beta1 in the conditioned media did not differ between 5.5 and 20 mM glucose. However, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not. This increased expression of the TGF-beta receptor type II was prevented by LY333531. These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the accelerated proliferation of SMCs under a high glucose condition, leading to the development of diabetic macroangiopathy.
Yasuda
Y
Y
Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Nakamura
J
J
Hamada
Y
Y
Nakayama
M
M
Chaya
S
S
Naruse
K
K
Nakashima
E
E
Kato
K
K
Kamiya
H
H
Hotta
N
N
D030201:Activin Receptors, Type I; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C099154:ruboxistaurin; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D005947:Glucose