Sirvent Audrey, Claudel Thierry, Martin Geneviève, Brozek John, Kosykh Vladimir, Darteil Raphaël, Hum Dean W, Fruchart Jean-Charles, Staels Bart
GENFIT, Parc Eurasanté, Loos, France.
FEBS Lett. 2004 May 21;566(1-3):173-7. doi: 10.1016/j.febslet.2004.04.026.
The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 cells treated with the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a significant increase of transcript level of the very low density lipoprotein receptor (VLDLR) was observed. Our data, resulting from selective FXR activation, FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up-regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human and in vivo in mouse liver cells.
法尼酯X受体(FXR)是一种由胆汁酸(BAs)激活的核受体。响应配体结合,FXR调节许多参与胆汁酸、脂质和脂蛋白代谢的基因。为了鉴定新的FXR靶基因,利用微阵列技术对用天然FXR激动剂鹅去氧胆酸(CDCA)处理的HepG2细胞中提取的总RNA进行分析。有趣的是,观察到极低密度脂蛋白受体(VLDLR)转录水平显著增加。我们通过选择性FXR激活、FXR RNA沉默和FXR缺陷小鼠得到的数据清楚地表明,胆汁酸在体外人肝细胞和体内小鼠肝细胞中通过FXR依赖性机制上调VLDLR转录水平。