title: Deoxycholic acid is involved in the proliferation and migration of vascular smooth muscle cells.
abstract: Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.
authors: Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University.
authors: Hidehisa
authors: H
authors: Shimizu
authors: Masahito
authors: M
authors: Hagio
authors: Hitoshi
authors: H
authors: Iwaya
authors: Ikuya
authors: I
authors: Tsuneki
authors: Ja-Young
authors: JY
authors: Lee
authors: Satoru
authors: S
authors: Fukiya
authors: Atsushi
authors: A
authors: Yokota
authors: Hitoshi
authors: H
authors: Miyazaki
authors: Hiroshi
authors: H
authors: Hara
authors: Satoshi
authors: S
authors: Ishizuka
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D001665:Binding Sites; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000009:adverse effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D003840:Deoxycholic Acid; D020797:Receptor, Platelet-Derived Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases