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Cell Type-specific Gene Expression Profiling in the Mouse Liver
10:06

Cell Type-specific Gene Expression Profiling in the Mouse Liver

Published on: September 17, 2019

The farnesoid X receptor induces fetuin-B gene expression in human hepatocytes

Takeshi Murakami1, Robert Walczak, Sandrine Caron

  • 1Tokyo New Research Laboratories I, Pharmaceutical Division, Kowa Company Ltd, 2-17-43 Noguchicho, Higashimurayama, Tokyo, Japan.

The Biochemical Journal
|July 28, 2007
PubMed

Insights

Human fetuin-B is a newly discovered target gene of the farnesoid X receptor (FXR). FXR activation increases fetuin-B expression in human liver cells, highlighting a new role for FXR in metabolic regulation.

Area of Science:

  • Molecular Endocrinology
  • Hepatology
  • Metabolic Regulation

Background:

  • The farnesoid X receptor (FXR) is a nuclear receptor crucial for regulating bile acid, lipid, and carbohydrate metabolism.
  • Recent advancements in synthetic FXR agonists and knockout models facilitate the identification of FXR target genes.

Purpose of the Study:

  • To identify novel FXR target genes.
  • To investigate the role of FXR in regulating human fetuin-B expression.

Main Methods:

  • Treatment of human primary hepatocytes and HepG2 cells with FXR agonists.
  • FXR knockdown using siRNA.
  • Analysis of alternative promoter usage (P1 and P2) in the human fetuin-B gene.
  • Identification and functional analysis of putative FXR-response elements (IR-1) using in vitro binding assays and transient transfection reporter assays.

Main Results:

  • FXR agonists significantly increased human fetuin-B expression in human hepatocytes and HepG2 cells.
  • FXR knockdown abolished FXR agonist-induced fetuin-B expression.
  • Human fetuin-B is transcribed from an alternative P2 promoter, which is induced by FXR agonists.
  • Two IR-1 motifs upstream of the P2 promoter were identified as functional FXR-response elements, mediating FXR-RXR complex binding and activation.

Conclusions:

  • Human fetuin-B is a novel FXR target gene in human hepatocytes.
  • FXR regulates human fetuin-B expression primarily through the P2 promoter via specific IR-1 response elements.
  • This finding expands the understanding of FXR's regulatory network in liver metabolism.

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