Houten Sander M, Auwerx Johan
Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
Ann Med. 2004;36(7):482-91. doi: 10.1080/07853890410018790.
Recent studies have established that bile salts are signaling molecules, besides their classic function in dietary lipid absorption and cholesterol metabolism. Bile salts signal by activating mitogen-activated protein kinase (MAPK) pathways and nuclear receptors like farnesoid X receptor-alpha (FXRalpha). FXRalpha activation increases the expression of direct FXRalpha target genes involved in bile salt transport and detoxification, and decreases expression of indirect FXRalpha target genes involved in bile salt biosynthesis and uptake. These actions prevent toxic accumulation of bile salts in the enterohepatic organs. A network of interactions with other nuclear receptors and MAPK pathways may protect the liver against pathological elevation of bile salts and cholestasis. Therefore treatment of cholestasis might benefit from the development of FXRalpha agonists.
最近的研究表明，除了在膳食脂质吸收和胆固醇代谢中的经典功能外，胆盐还是信号分子。胆盐通过激活丝裂原活化蛋白激酶（MAPK）途径和类法尼醇X受体α（FXRα）等核受体来发出信号。FXRα的激活增加了参与胆盐转运和解毒的直接FXRα靶基因的表达，并降低了参与胆盐生物合成和摄取的间接FXRα靶基因的表达。这些作用可防止胆盐在肠肝器官中的毒性积累。与其他核受体和MAPK途径的相互作用网络可能保护肝脏免受胆盐病理性升高和胆汁淤积的影响。因此，胆汁淤积的治疗可能受益于FXRα激动剂的开发。
