Functional evolution of the vitamin D and pregnane X receptors
Author Information
Author(s): Erica J Reschly, Bainy Afonso Celso Dias, Jaco Joaquim Mattos, Lee R Hagey, Nathan Bahary, Sripal R Mada, Junhai Ou, Raman Venkataramanan, Matthew D Krasowski
Primary Institution: University of Pittsburgh
Hypothesis
How do the ligand selectivities of vitamin D receptors (VDRs) compare across different vertebrate species and what evidence exists for PXR-mediated effects in non-mammalian species?
Conclusion
The study shows that VDR ligand selectivity is highly conserved across vertebrate species, while classic PXR-mediated effects were only observed in zebrafish and not in sea lamprey or African clawed frog.
Supporting Evidence
- VDRs from various vertebrates showed similar ligand selectivities for vitamin D derivatives.
- Zebrafish demonstrated PXR-mediated induction of enzyme expression in response to known PXR activators.
- Analysis of the sea lamprey genome did not reveal evidence of a PXR gene.
Takeaway
This study looks at how different animals use vitamin D and pregnane X receptors, finding that while many animals use vitamin D in similar ways, zebrafish are unique in how they respond to certain chemicals.
Methodology
The study compared ligand selectivities of VDRs across vertebrate species and assessed PXR-mediated effects using primary hepatocyte cultures and in vivo models.
Limitations
The study's findings regarding PXR in sea lamprey are limited by the preliminary nature of the genomic data available.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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