A novel adipocytokine, vaspin inhibits platelet-derived growth factor-BB-induced migration of vascular smooth muscle cells.
Vaspin is a novel adipocytokine originally identified in visceral white adipose tissues of Otsuka Long-Evans Tokushima fatty rats, an animal model of type 2 diabetes. We have previously shown that vaspin has anti-inflammatory effects in vascular smooth muscle cells (SMCs). SMCs migration is an important process for development atherosclerosis. However, effects of vaspin on SMCs migration remain to be clarified. Rat mesenteric arterial SMCs were treated with platelet-derived growth factor (PDGF)-BB (10 ng/ml, 90 min) in the absence or presence of vaspin (0.01-10 ng/ml, pretreatment for 2h). SMCs migration was evaluated by a Boyden chamber assay. Western blotting was performed to analyze cellular signals. Reactive oxygen species (ROS) generation was fluorometrically measured using 2',7'-dichlorofluorescein diacetate. Vaspin significantly inhibited PDGF-BB-induced SMCs migration. Vaspin significantly inhibited PDGF-BB-induced phosphorylation of p38 and heat shock protein (HSP) 27 as well as ROS generation. SMCs migration was blocked by an inhibitor of p38 or an anti-oxidant drug, N-acetyl-l-cysteine (NAC). NAC significantly inhibited the PDGF-BB-induced phosphorylation of p38 and HSP27. In addition, vaspin inhibited PDGF-BB-induced actin cytoskeletal reorganization (lamellipodia formation) as revealed by a rhodamine phalloidin staining. The present study for the first time revealed that vaspin inhibits PDGF-BB-induced SMCs migration through inhibiting p38/HSP27 signals via preventing the ROS generation.
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
Sukanya
S
Phalitakul
Muneyoshi
M
Okada
Yukio
Y
Hara
Hideyuki
H
Yamawaki
D000111:Acetylcysteine / Q000494:pharmacology; D054392:Adipokines / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D017382:Reactive Oxygen Species / Q000378:metabolism; D015843:Serpins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D054392:Adipokines; D000975:Antioxidants; D055551:HSP27 Heat-Shock Proteins; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; C506516:Serpina12 protein, rat; D015843:Serpins; D000077214:Becaplermin; D048051:p38 Mitogen-Activated Protein Kinases; D000111:Acetylcysteine