法尼甾体X受体
胆汁酸
G蛋白偶联胆汁酸受体
FGF19型
胆固醇7α羟化酶
结肠炎
下调和上调
过氧化物酶体增殖物激活受体
核受体
化学
胆盐出口泵
牛磺胆酸
刺猬信号通路
过氧化物酶体
内科学
受体
内分泌学
生物化学
生物
信号转导
医学
转录因子
运输机
成纤维细胞生长因子
基因
作者
Xueyan Zhou,Lijuan Cao,Changtao Jiang,Yang Xie,Xuefang Cheng,Kristopher W. Krausz,Yunpeng Qi,Lu Sun,Yatrik M. Shah,Frank J. Gonzalez,Guangji Wang,Haiping Hao
摘要
Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis. Dextran sulphate sodium (DSS)-induced colitis leads to accumulation of bile acids in inflamed colon tissues via activation of the intestinal peroxisome PPARα-UGTs pathway. UGTs accelerate the metabolic elimination of bile acids, and thereby decrease their intracellular levels in the small intestine. Reduced intracellular bile acids results in repressed farnesoid X receptor (FXR)-FGF15 signalling, leading to upregulation of hepatic CYP7A1, thus promoting the de novo bile acid synthesis. Both knockout of PPARα and treatment with recombinant FGF19 markedly attenuate DSS-induced colitis. Thus, we propose that intestinal PPARα-UGTs and downstream FXR-FGF15 signalling play vital roles in control of bile acid homeostasis and the pathological development of colitis. Bile acids have been linked to the development of inflammatory bowel diseases, such as colitis. Here the authors show that bile acid levels in mice are controlled by a circular feedback system involving the nuclear receptors PPARα and FXR, and that this system is dysregulated in colitis.
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