Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.
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.
Huang
Wendong
W
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Ma
Ke
K
Zhang
Jun
J
Qatanani
Mohammed
M
Cuvillier
James
J
Liu
Jun
J
Dong
Bingning
B
Huang
Xiongfei
X
Moore
David D
DD
D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002452:Cell Count; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000494:pharmacology; D019826:Cholic Acid / Q000008:administration & dosage; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016259:Genes, myc; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D006706:Homeostasis; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D002792:Cholestyramine Resin; D019826:Cholic Acid; D016207:Cytokines; D004268:DNA-Binding Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D006133:Growth Substances; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C491524:Foxm1 protein, mouse; C489428:Myc protein, mouse; C099713:nuclear receptor subfamily 0, group B, member 2; C502772:Cyp7a1 protein, mouse