Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice.
Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is the primary bile acid receptor. We previously showed that FXR was required for the promotion of liver regeneration/repair after physical resection or liver injury. However, the mechanism by which FXR promotes liver regeneration/repair is still unclear. Here we show that both hepatic-FXR and intestine-FXR contributed to promote liver regeneration/repair after either 70% partial hepatectomy or carbon tetrachloride-induced liver injury. Hepatic FXR, but not intestine FXR, is required for the induction of Foxm1b gene expression in liver during liver regeneration/repair. In contrast, intestine FXR is activated to induce FGF15 expression in intestine after liver damage. Ectopic expression of FGF15 was able to rescue the defective liver regeneration/repair in intestine-specific FXR null mice.


CONCLUSIONS
These results demonstrate that, in addition to the cell-autonomous effect of hepatic FXR, the endocrine FGF15 pathway activated by FXR in intestine also participates in the promotion of liver regeneration/repair.
Division of Gene Regulation and Drug Discovery, Department of Diabetes and Metabolic Diseases, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Lisheng
L
Zhang
Yan-Dong
YD
Wang
Wei-Dong
WD
Chen
Xichun
X
Wang
Guiyu
G
Lou
Nian
N
Liu
Min
M
Lin
Barry M
BM
Forman
Wendong
W
Huang
D000704:Analysis of Variance; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006498:Hepatectomy; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002251:Carbon Tetrachloride; D002790:Cholesterol 7-alpha-Hydroxylase; D005346:Fibroblast Growth Factors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C108526:fibroblast growth factor 15, mouse; C502772:Cyp7a1 protein, mouse