Department of Gastroenterology, Imperial College NHS Trust, Hammersmith Hospital, Section of Hepatology & Gastroenterology, Imperial College, London, W12 0HS, UK.
Expert Rev Gastroenterol Hepatol. 2013 Jan;7(1):49-56. doi: 10.1586/egh.12.66.
The role of bile acids (BA) extends far beyond lipid digestion and cholesterol metabolism. The transcriptional regulation of multiple genes within the liver and intestine are under their influence. BA exert these effects through binding and activating receptors in much the same way as endocrine hormones. The farnesoid X receptor (FXR) is the intracellular transcription factor for BA; TGR5 is the cell-surface receptor. The main target genes of FXR are those involved in BA and cholesterol metabolism. Yet more recently, FXR has also been shown to influence and promote certain protective pathways within the liver. These pathways are being harnessed by semisynthetic BAs in Phase II and III clinical trials. FXR activation within the intestine is also associated with similar protective pathways. This article examines the consequences of altered FXR activation in the context of BA malabsorption in Crohn's disease and the potential benefits of FXR agonists in Crohn's disease.
胆汁酸（BA）的作用远不止于脂质消化和胆固醇代谢。肝脏和肠道内的多种基因的转录调控都受到其影响。BA 通过与内分泌激素类似的方式结合并激活受体来发挥这些作用。法尼醇 X 受体（FXR）是 BA 的细胞内转录因子；TGR5 是细胞表面受体。FXR 的主要靶基因是那些参与 BA 和胆固醇代谢的基因。然而，最近还发现 FXR 也可以影响和促进肝脏内的某些保护途径。这些途径正在 II 期和 III 期临床试验中被半合成 BA 利用。肠道内的 FXR 激活也与类似的保护途径有关。本文探讨了在克罗恩病中 BA 吸收不良的情况下改变 FXR 激活的后果，以及 FXR 激动剂在克罗恩病中的潜在益处。
