Gadaleta Raffaella M, van Mil Saskia W C, Oldenburg Bas, Siersema Peter D, Klomp Leo W J, van Erpecum Karel J
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Biochim Biophys Acta. 2010 Jul;1801(7):683-92. doi: 10.1016/j.bbalip.2010.04.006. Epub 2010 Apr 23.
The nuclear receptor Farnesoid X Receptor (FXR) critically regulates nascent bile formation and bile acid enterohepatic circulation. Bile acids and FXR play a pivotal role in regulating hepatic inflammation and regeneration as well as in regulating extent of inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. Recent evidence suggests, that the bile acid-FXR interaction is involved in the pathophysiology of a wide range of diseases of the liver, biliary and gastrointestinal tract, such as cholestatic and inflammatory liver diseases and hepatocellular carcinoma, inflammatory bowel disease and inflammation-associated cancer of the colon and esophagus. In this review we discuss current knowledge of the role the bile acid-FXR interaction has in (patho)physiology of the liver, biliary and gastrointestinal tract, and proposed underlying mechanisms, based on in vitro data and experimental animal models. Given the availability of highly potent synthetic FXR agonists, we focus particularly on potential relevance for human disease.
核受体法尼醇X受体（FXR）对新生胆汁形成和胆汁酸肝肠循环起着关键的调节作用。胆汁酸和FXR在调节肝脏炎症和再生以及调节炎症反应程度、肠道屏障功能和预防细菌易位方面发挥着关键作用。最近的证据表明，胆汁酸与FXR的相互作用参与了肝脏、胆道和胃肠道多种疾病的病理生理学过程，如胆汁淤积性和炎症性肝病、肝细胞癌、炎症性肠病以及结肠和食管癌等炎症相关癌症。在本综述中，我们基于体外数据和实验动物模型，讨论了胆汁酸与FXR相互作用在肝脏、胆道和胃肠道（病理）生理学中的作用的现有知识，并提出了潜在的作用机制。鉴于高效合成FXR激动剂的可得性，我们特别关注其对人类疾病的潜在相关性。
