The farnesoid X receptor induces very low density lipoprotein receptor gene expression

The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 ce...

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Bibliographic Details
Published in:FEBS letters 2004-05, Vol.566 (1), p.173-177
Main Authors: Sirvent, Audrey, Claudel, Thierry, Martin, Geneviève, Brozek, John, Kosykh, Vladimir, Darteil, Raphaël, Hum, Dean W., Fruchart, Jean-Charles, Staels, Bart
Format: Article
Language:English
Subjects:
Animals
apo, apolipoprotein
BA, bile acid
Bile Acids and Salts - pharmacology
BSEP, bile salt export pump
CDCA, chenodeoxycholic acid
Cell Line, Tumor
Chenodeoxycholic Acid - pharmacology
DNA-Binding Proteins - agonists
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
FA, fatty acid
Farnesoid X receptor
FGF, fibroblast growth factor
FXR, farnesoid X receptor
FXRE, FXR response element
HDL, high density lipoprotein
Hepatocytes - metabolism
Humans
I-BABP, intestinal bile acid binding protein
IR, inverted repeat
Isoxazoles - pharmacology
Liver - metabolism
LPL, lipoprotein lipase
LRH, liver receptor homolog
Male
MDR, multidrug resistance gene
Mice
Mice, Inbred C57BL
Mice, Knockout
Microarray analysis
NTCP, Na+-taurocholate transporting polypeptide
PFIC, progressive familial intrahepatic cholestasis
PLTP, phospholipid transfer protein
PPAR, peroxisome proliferator-activated receptor
Receptors, Cytoplasmic and Nuclear
Receptors, LDL - biosynthesis
Receptors, LDL - genetics
RNA, Small Interfering - pharmacology
SHP, small heterodimer partner
siRNA, small interfering RNA
Small interfering RNA
TCA, taurocholic acid
TG, triglyceride
Time Factors
Transcription Factors - agonists
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - physiology
Transcription, Genetic - drug effects
Transcription, Genetic - physiology
Transfection
Up-Regulation - drug effects
VLDL receptor
VLDLR, very low density lipoprotein receptor
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Summary:The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 cells treated with the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a significant increase of transcript level of the very low density lipoprotein receptor (VLDLR) was observed. Our data, resulting from selective FXR activation, FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up-regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human and in vivo in mouse liver cells.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2004.04.026