title: A novel adipocytokine, omentin, inhibits platelet-derived growth factor-BB-induced vascular smooth muscle cell migration through antioxidative mechanism.
abstract: Omentin is a novel adipocytokine expressed in visceral adipose tissue. Secretion and blood concentration of omentin decrease in the obese subjects. We previously demonstrated that omentin is anti-inflammatory in vascular smooth muscle cells (SMCs). While vascular remodeling via migration of SMCs is also important for hypertension development, it remains to be clarified whether omentin affects this process. Here we examined whether omentin controls SMC migration. Omentin (300 ng/ml, 2 h) significantly inhibited platelet-derived growth factor (PDGF)-BB (10 ng/ml, 6 h)-induced migration of rat mesenteric arterial SMCs, as determined by Boyden chamber assay. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB (10 ng/ml, 30 min)-induced phosphorylation of p38 and heat shock protein (HSP) 27. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB (10 ng/ml, 30 min)-induced NADPH oxidase (NOX) activation as determined by lucigenin assay. Omentin (300 ng/ml, 24 h) significantly inhibited fetal bovine serum (5%, 4 days)-induced SMC outgrowth from rat isolated mesenteric artery. In vivo, omentin significantly inhibited carotid intimal hyperplasia in mouse ligation model. In summary, we for the first time demonstrate that omentin prevents PDGF-BB-induced SMC migration by preventing NOX/O2(-)/p38/HSP27 pathways, which might be at least partly responsible for the preventive effects on neointimal hyperplasia. Our data suggest that omentin may be protective against hypertension development by inhibiting vascular structural remodeling.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Kazama
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan yamawaki@vmas.kitasato-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
mesh_terms: D054392:Adipokines / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D000077214:Becaplermin; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D058851:GPI-Linked Proteins; D055551:HSP27 Heat-Shock Proteins / Q000502:physiology; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D019255:NADPH Oxidases / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D054392:Adipokines; D000975:Antioxidants; D016207:Cytokines; D058851:GPI-Linked Proteins; D055551:HSP27 Heat-Shock Proteins; C000591993:Itln1 protein, mouse; D037102:Lectins; D020574:Proto-Oncogene Proteins c-sis; C000591992:omentin protein, rat; D000077214:Becaplermin; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; D010100:Oxygen
keywords: adipokine; cell signaling; migration; oxidative stress; vascular smooth muscle