Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.
Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.
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DOI：
10.1186/1476-511x-13-50
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发表时间：
2014-03-19
影响因子：
4.5
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Zhao JY;Hu YW;Li SF;Hu YR;Ma X;Wu SG;Wang YC;Gao JJ;Sha YH;Zheng L;Wang Q
载脂蛋白M（apoM）作为一种新型载脂蛋白，主要在肝、肾组织中表达，与动脉粥样硬化和糖尿病的发生发展密切相关。我们的研究小组最近表明，二氢辣椒素 (DHC) 可以显着减少 apoE−/− 小鼠的动脉粥样硬化斑块形成。然而，DHC对apoM表达的影响和可能的机制仍不清楚。 HepG2细胞分别用0μM、25μM、50μM和100μM DHC处理24小时或用100μM DHC处理0、6、12和24小时。分别通过实时定量PCR和蛋白质印迹分析测量mRNA水平和蛋白质水平。我们发现DHC以剂量依赖性和时间依赖性的方式显着降低HepG2细胞中apoM的mRNA和蛋白质水平的表达。在HepG2细胞中，DHC处理后Foxa2的表达降低，而LXRα的表达增加。此外，Foxa2的过表达显着补偿了DHC对apoM表达的抑制作用。 LXRα小干扰RNA显着消除了DHC对apoM表达的抑制作用。用DHC处理的C57BL/6小鼠的肝脏apoM表达显着降低。此外，肝脏中 Foxa2 的表达较低，而 LXRα 的表达较高。 DHC可以通过抑制HepG2细胞中Foxa2的表达并增强LXRα的表达来下调apoM的表达。
Apolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE−/− mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear. HepG2 cells were treated with 0 μM, 25 μM, 50 μM and 100 μM DHC for 24 h or were treated with 100 μM DHC for 0, 6, 12, and 24 h, respectively. The mRNA levels and protein levels were measured by real-time quantitative PCR and western blot analysis, respectively. We found that DHC markedly decreased expression of apoM at both mRNA and protein level in HepG2 cells in a dose-dependent and time-dependent manner. Expression of Foxa2 was decreased while expression of LXRα was increased by DHC treatment in HepG2 cells. In addittion, overexpression of Foxa2 markedly compensated the inhibition effect induced by DHC on apoM expression. LXRα small interfering RNA significantly abolished the inhibition effect which induced by DHC on apoM expression. The liver of C57BL/6 mice treated with DHC had significantly lower expression of apoM. Furthermore, the liver had lower expression of Foxa2 while had higher expression of LXRα. DHC could down-regulate apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.