Gene Expression Profiling of 1????,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73612949" target="_blank" >RIV/61989592:15310/22:73612949 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202200070" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202200070</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/mnfr.202200070" target="_blank" >10.1002/mnfr.202200070</a>
Alternative languages
Result language
angličtina
Original language name
Gene Expression Profiling of 1????,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes
Original language description
Scope CYP3A4 is the most important drug-metabolizing enzyme regulated via the vitamin D receptor (VDR) in the intestine. However, less is known about VDR in the regulation of CYP3A4 and other drug-metabolizing enzymes in the liver. Methods and Results This study investigates whether 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) regulates major cytochrome P450 enzymes, selected phase I and II enzymes, and transporters involved in xenobiotic and steroidal endobiotic metabolism in 2D and 3D cultures of human hepatocytes. The authors found that 1 alpha,25(OH)(2)D-3 increases hepatic CYP3A4 expression and midazolam 1 '-hydroxylation activity in 2D hepatocytes. The results are confirmed in 3D spheroids, where 1 alpha,25(OH)(2)D-3 has comparable effect on CYP3A4 mRNA expression as 1 alpha-hydroxyvitamin D-3, an active vitamin D metabolite. Other regulated genes such as CYP1A2, AKR1C4, SLC10A1, and SLCO4A1 display only mild changes in mRNA levels after 1 alpha,25(OH)(2)D-3 treatment in 2D hepatocytes. Expression of other cytochrome P450, phase I and phase II enzyme, or transporter genes are not significantly influenced by 1 alpha,25(OH)(2)D-3. Additionally, the effect of VDR activation on CYP3A4 mRNA expression is abolished by natural dietary compound sulforaphane, a common suppressor of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Conclusion This study proposes that VDR or vitamin D supplementation is unlikely to significantly influence liver detoxification enzymes apart from CYP3A4.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10700 - Other natural sciences
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
MOLECULAR NUTRITION & FOOD RESEARCH
ISSN
1613-4125
e-ISSN
1613-4133
Volume of the periodical
66
Issue of the periodical within the volume
9
Country of publishing house
DE - GERMANY
Number of pages
17
Pages from-to
"2200070-1"-"2200070-17"
UT code for WoS article
000762216200001
EID of the result in the Scopus database
2-s2.0-85125352623