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Science 312 (5771): 233-236

Copyright © 2006 by the American Association for the Advancement of Science

Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration

Wendong Huang,1* Ke Ma,1 Jun Zhang,1{dagger} Mohammed Qatanani,1{ddagger} James Cuvillier,1 Jun Liu,1 Bingning Dong,1 Xiongfei Huang,2 David D. Moore1§

Abstract: Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor–dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.

1 Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
2 Department of Gene Regulation and Drug Discovery, City of Hope Beckman Research Institute, 1500 East Duarte, Duarte, CA 91010, USA.

* Present address: Department of Gene Regulation and Drug Discovery, City of Hope Beckman Research Institute, 1500 East Duarte, Duarte, CA 91010, USA.

{dagger} Present address: Clark Center W252, 318 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.

{ddagger} Present address: Division of Endocrinology, Diabetes, and Metabolism, and University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.

§ To whom correspondence should be addressed. E-mail: moore{at}bcm.tmc.edu

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