Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19

@article{Miyata2012InvolvementOM,
  title={Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19
},
  author={Masaaki Miyata and Tatsuya Hata and Hiroki Yamakawa and Tatehiro Kagawa and Kouichi Yoshinari and Yasushi Yamazoe},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  year={2012},
  volume={132},
  pages={41-47}
}
  • M. Miyata, T. Hata, Y. Yamazoe
  • Published 1 October 2012
  • Biology, Chemistry
  • The Journal of Steroid Biochemistry and Molecular Biology
SREBP-2 negatively regulates FXR-dependent transcription of FGF19 in human intestinal cells.
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TLDR
Using reporter gene assays with several deletion constructs, it is found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two potential binding sites for PXR.
Unveiling a New Essential Cis Element for the Transactivation of the CYP3A4 Gene by Xenobiotics
TLDR
HepG2-based transactivation assays with the reporter gene constructs with or without mutations in the PXR binding element(s) demonstrated that this DR4 motif is essential for the transcriptional activation not only by rifampicin but also by various human PxR activators.
Fibroblast growth factor 19 treatment ameliorates disruption of hepatic lipid metabolism in farnesoid X receptor (Fxr)-null mice.
TLDR
Results indicate that FGF19-mediated signaling ameliorates disrupted hepatic lipogenesis in Fxr-null mice.
Fibroblast Growth Factor-19, a Novel Factor That Inhibits Hepatic Fatty Acid Synthesis*
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The inhibitory effect of FGF-19 on insulin activation of hepatic fatty acid synthesis constitutes a mechanism that would explain the beneficial effect of PGC-1β on metabolic syndrome and inhibition of gene transcription by an elevation in SHP expression can explain the inhibition of lipogenic enzyme expression.
Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis.
TLDR
It is demonstrated that FXR directly regulates expression of fibroblast growth factor-19 (FGF-19), a secreted growth factor that signals through the FGFR4 cell-surface receptor tyrosine kinase, which defines a novel mechanism for feedback repression of bile acid biosynthesis.
FGF15/FGFR4 Integrates Growth Factor Signaling with Hepatic Bile Acid Metabolism and Insulin Action*
TLDR
Observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism.
Genome‐wide tissue‐specific farnesoid X receptor binding in mouse liver and intestine
TLDR
This study reports genome‐wide FXR binding in vivo and the results clearly demonstrate tissue‐specific FXR/gene interaction, indicating that FXR may be involved in regulating broader biological pathways in maintaining hepatic and intestinal homeostasis.
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