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Farnesoid X receptor, the bile acid sensing nuclear receptor, in liver regeneration

Authors :
Guodong Li
Grace L. Guo
Source :
Acta Pharmaceutica Sinica. B, Acta Pharmaceutica Sinica B, Vol 5, Iss 2, Pp 93-98 (2015)
Publication Year :
2014

Abstract

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.<br />Graphical abstract This review focuses on the roles of bile acids (BAs) and farnesoid X receptor (FXR) in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

Subjects

Subjects :
WT, wild type
CYP8B1, sterol 12α-hydroxylase
STAT3, signal transducer and activator of transcription 3
Review
C/EBPβ, CCAAT-enhancer binding protein β
SHP, small heterodimer partner
General Pharmacology, Toxicology and Pharmaceutics
CTX, cerebrotendinous xanthomatosis
Rb, retinoblastoma
CA, cholic acid
GPBAR1 or TGR5, G protein-coupled BA receptor 1
Bile acid
THR, TH receptor
ABC, ATP-binding cassette
DDAH-1, dimethylarginineaminohydrolase-1
Liver regeneration
MRP3, multidrug resistance associated protein 3
Fibroblast growth factor 15
3. Good health
cAMP, cyclic adenosine monophosphate
TH, thyroid hormone
Biochemistry
JNK, c-Jun N-terminal kinase
BA, bile acid
hepFxr-KO, hepatocyte-specific Fxr knockout
NASH, nonalcoholic steatohepatitis
Liver-intestine cross talk
medicine.drug_class
PH, partial hepatectomy
NF-κB, nuclear factor-κB
Biology
Cholesterol 7 alpha-hydroxylase
CCAAT-Enhancer-Binding Protein-beta
CDCA, chenodeoxycholic acid
FXR, farnesoid X receptor
Liver-intestine croass talk
Farnesoid X receptor
Transmembrane G protein coupled receptor 5
medicine
HEX, hematopoietically expressed homeobox
FGFR4, FGF receptor 4
Liver X receptor
KC, Kupffer cells
FGF-15, fibroblast growth factor 15
KO, knockout
lcsh:RM1-950
CYP7A1, cholesterol 7alpha-hydroxylase
ERK1/2, extracellular signal-regulated kinase 1/2
FOXM1b, forkhead boxm1b
Fxr-KO, Fxr-knockout
Bile acids
AMPK, AMP-activated protein kinase
lcsh:Therapeutics. Pharmacology
Nuclear receptor
CYP8B1
MAPK, mitogen-activated protein kinase
Cyp27-KO, sterol 27-hydroxylase–knockout

Details

ISSN :
22113835
Volume :
5
Issue :
2
Database :
OpenAIRE
Journal :
Acta pharmaceutica Sinica. B
Accession number :
edsair.doi.dedup.....9b0113b1505196c1f0fbca2d11d05f75