Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells

DOI Web Site PubMed 被引用文献1件 参考文献23件
  • SHIMIZU Hidehisa
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • HAGIO Masahito
    Faculty of Life Sciences, Toyo University
  • IWAYA Hitoshi
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • TSUNEKI Ikuya
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • LEE Ja-Young
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • FUKIYA Satoru
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • YOKOTA Atsushi
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • MIYAZAKI Hitoshi
    Graduate School of Life and Environmental Sciences, University of Tsukuba
  • HARA Hiroshi
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University
  • ISHIZUKA Satoshi
    Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University

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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.

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