Redundant Pathways for Negative Feedback Regulation of Bile Acid Production
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-α-hydroxylase expression in respon...
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Published in | Developmental cell Vol. 2; no. 6; pp. 721 - 731 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.06.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 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-α-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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/S1534-5807(02)00187-9 |