Expression of ANGPTL3 regulated by NR1H2 or NR1H3

The angiopoietin-Like 3 (ANGPTL3) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. ANGPTL3 is a direct target gene of the LXR:RXR heterodimer. Synthetic and endogenous oxysterol ligand administration to human HepG2 cells or mice results in increased mRNA and protein levels of ANGPTL3 (Kaplan R et al. 2003). An LXR response element (LXRE) was identified in the promoter of human ANGPTL3 which conferred ligand and receptor-specific regulation in luciferase cell reporter assays (Kaplan R et al. 2003). ANGPTL3 is a secreted protein that inhibits activity of lipoprotein lipase and endothelial lipase (Shimizugawa T et al. 2002), and the LXR-mediated upregulation of this gene likely contributes (along with hepatic lipogenesis) to the severe hypertriglyceridemia associated with use of LXR drugs (Inaba T et al. 2003)

血管生成素样3（ANGPTL3）基因经过转录产生mRNA，随后mRNA被翻译成蛋白质。ANGPTL3是大类固醇受体（LXR）:RXR异源二聚体的直接靶基因。对人类HepG2细胞或小鼠施用合成和内源性的氧化固醇配体，会导致ANGPTL3的mRNA和蛋白质水平升高（Kaplan R 等人，2003年）。在人类ANGPTL3的启动子区域中鉴定出LXR反应元件（LXRE），该元件在荧光素酶细胞报告实验中赋予配体和受体特异性调控（Kaplan R 等人，2003年）。ANGPTL3是一种分泌蛋白，可抑制脂蛋白脂肪酶和内皮脂肪酶的活性（Shimizugawa T 等人，2002年），LXR介导的该基因上调可能与使用LXR药物相关的严重高甘油三酯血症有关（Inaba T 等人，2003年）