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FEBS Lett. 2017 Oct;591(20):3360-3368. doi: 10.1002/1873-3468.12845. Epub 2017 Oct 11.

FXR controls CHOP expression in steatohepatitis.

Author information

1
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
2
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.

Abstract

The farnesoid X receptor (FXR) and C/EBP homologous protein (CHOP) have critical functions in hepatic lipid metabolism. Here, we aimed to explore a potential relationship between FXR and CHOP. We fed wild-type (WT) and FXR KO mice a MCD diet (model of steatohepatitis) and found that Chop mRNA expression is upregulated in WT but not FXR KO mice. The absence of FXR aggravates hepatic inflammation after MCD feeding. In HepG2 cells, we found that Chop expression is regulated in a FXR/Retinoid X receptor (RXR)-dependent manner. We identified a FXR/RXR-binding site in the human CHOP promoter, demonstrating a highly conserved regulatory pathway. Our study shows that FXR/RXR regulates Chop expression in a mouse model of steatohepatitis, providing novel insights into pathogenesis of this disorder.

KEYWORDS:

inflammation; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); nuclear receptor

PMID:
28895119
PMCID:
PMC5698708
DOI:
10.1002/1873-3468.12845
[Indexed for MEDLINE]
Free PMC Article

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