title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Arita
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Muraguchi
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: 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
chemical_list: 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