Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells
Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells
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DOI：
10.3177/jnsv.60.450
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发表时间：
2014-12-01
影响因子：
1.6
通讯作者：
Ishizuka, Satoshi
中科院分区：
文献类型：
--
作者：
Shimizu, Hidehisa;Hagio, Masahito;Ishizuka, Satoshi
肥胖越来越多地与动脉粥样硬化的风险增加有关。高脂饮食诱导的肥胖小鼠血清中胆汁酸脱氧胆酸（DCA）水平升高。因此，我们研究了DCA对血管平滑肌细胞（VSMC）功能的影响，因为动脉粥样硬化的发生和发展与VSMC的增殖和迁移有关。DCA诱导c-jun N-末端激酶（JNK）激活，而JNK抑制剂阻止DCA诱导的VSMC增殖和迁移。基于这些发现，我们研究了DCA是否促进血小板源性生长因子β受体（PDGFR β）的表达，该受体在其启动子区具有c-Jun结合位点。在与DCA孵育24和48小时后，VSMC中PDGFR β的mRNA和蛋白表达水平分别上调。尽管在PDGF刺激期间没有DCA，但与DCA孵育48小时后，PDGF的作用如VSMCs的增殖和迁移得到促进。这些结果表明，DCA的血清浓度升高参与了HF诱导的肥胖症的动脉粥样硬化的发病机制。
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 beta-receptor (PDGFR beta) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFR beta 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.