Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.
BACKGROUND
Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods and Results- HASMC proliferation was estimated by [(3)H] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to (125)I-PDGF-BB and significantly inhibited the association of (125)I-PDGF-BB with HASMCs, but no effects were observed on the binding of (125)I-PDGF-AA or (125)I-heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular signal-related kinase (ERK) phosphorylation and PDGF beta-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA-stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF alpha-receptor or EGF receptor.


CONCLUSIONS
The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.
Arita
Yukio
Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka and First Institute of New Drug Research, Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan.
Kihara
Shinji
S
Ouchi
Noriyuki
N
Maeda
Kazuhisa
K
Kuriyama
Hiroshi
H
Okamoto
Yoshihisa
Y
Kumada
Masahiro
M
Hotta
Kikuko
K
Nishida
Makoto
M
Takahashi
Masahiko
M
Nakamura
Tadashi
T
Shimomura
Iichiro
I
Muraguchi
Masahiro
M
Ohmoto
Yasukazu
Y
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
D017667:Adipocytes / Q000737:chemistry; D052242:Adiponectin; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; D001798:Blood Proteins; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor; D000077214:Becaplermin; D020928:Mitogen-Activated Protein Kinases