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

  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},
  • 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.
Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives
Differences between mice and humans in the biology of FGF15/19 have to be considered for a successful translation from bench to bedside, with a special focus on regulation of production, morphogenic properties, hepatocyte growth, bile acid homeostasis, as well as actions on glucose, lipid, and energyHomeostasis.
Metabolic Messengers: fibroblast growth factor 15/19
The gut hormone FGF19 and its mouse orthologue Fgf15 are important mediators of the metabolic transition between the fasted and fed state and the putative therapeutic potential in areas of unmet medical need is discussed.
Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids
FGF19 expression in human ileum is very highly responsive to BA, and changes in FGF19 induction are a potential mechanism involved in disorders of BA homeostasis.
TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk
Comprehensive in vivo analysis revealed that TCF7L2 transcriptionally upregulates FGF15 in the gut, leading to reduced bile synthesis and diminished intestinal lipid uptake, indicating the relevance of TCF4‐dependent regulation of biles synthesis to human disease.
Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease.
Farnesoid X receptor and reproduction
Although the relevance of the FXRα on reproduction is widely unknown, its endogenous ligands like farnesol, chenodeoxycholic acid (CDCA), and cholate acid participate in proliferation, apoptosis, differentiation, and steroidogenesis in reproductive tissues.
Regulation of bile acid homeostasis by the intestinal Diet1–FGF15/19 axis
The biological effects of FGF15/19 make it an attractive target for treating metabolic dysregulation underlying conditions such as fatty liver and type 2 diabetes, and additional metabolic effects on glucose metabolism, nonalcoholic liver disease, and liver regeneration are highlighted.


Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR.
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
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.
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*
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.
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*
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
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.