Redundant pathways for negative feedback regulation of bile acid production
Redundant pathways for negative feedback regulation of bile acid production
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DOI：
10.1016/s1534-5807(02)00187-9
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发表时间：
2002-06-01
影响因子：
11.8
通讯作者：
Moore, DD
中科院分区：
文献类型：
--
作者：
Wang, L;Lee, YK;Moore, DD
孤儿核激素受体SHP已被提出在胆汁酸产生的负反馈调节中具有关键作用。与此相一致，缺乏SHP基因的小鼠表现出胆汁酸稳态的轻度缺陷，并且不能抑制胆固醇7-α-羟化酶表达以响应胆汁酸受体FXR的特异性激动剂。然而，这种抑制保留在SHP敲除小鼠喂养胆汁酸，证明存在胆汁酸信号传导的补偿性抑制途径。我们提供了两个这样的途径的证据，基于异生素受体PXR或c-Jun N-末端激酶JNK的激活。我们的结论是，冗余机制调节胆固醇稳态的这一关键方面。
The orphan nuclear hormone receptor SHP has been proposed to have a key role in the negative feedback regulation of bile acid production. Consistent with this, mice lacking the SHP gene exhibit mild defects in bile acid homeostasis and fail to repress cholesterol 7-alpha-hydroxylase expression in response to a specific agonist for the bile acid receptor FXR. However, this repression is retained in SHP null mice fed bile acids, demonstrating the existence of compensatory repression pathways of bile acid signaling. We provide evidence for two such pathways, based on activation of the xenobiotic receptor PXR or the c-Jun N-terminal kinase JNK. We conclude that redundant mechanisms regulate this critical aspect of cholesterol homeostasis.