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- W2134065514 abstract "Lipophilic bile acids are suggested to be involved in the endogenous expression of CYP3A4 in human and experimental animals as ligands of nuclear receptors. To verify the nuclear receptor specificity, the bile acid-mediated induction of CYP3A4 has been studied in vitro and in vivo in the present study. Lithocholic acid (LCA) strongly enhanced the activities of the <i>CYP3A4</i> reporter gene, which contained multiple nuclear receptor binding elements, in both HepG2 and LS174T cells. The introduction of small interfering RNA for human vitamin D receptor (VDR), but not for human pregnane X receptor, reduced the LCA-induced activation of the reporter gene in these cells, suggesting the major role of VDR in the LCA induction of CYP3A4. Consistently, oral administration of LCA (100 mg/kg/day for 3 days) increased Cyp3a protein levels in the intestine but not in the liver, where a negligible level of VDR mRNA is detected. The selective role of VDR was tested in mice with the adenoviral overexpression of the receptor. Oral administration of LCA had no clear influence on the <i>CYP3A4</i> reporter activity in the liver of control mice. In mice with the adenovirally expressed VDR, LCA treatment (100 or 400 mg/kg/day for 3 days) resulted in the enhanced reporter activities and increased levels of Cyp3a proteins in the liver. These results indicate the selective involvement of VDR, but not pregnane X receptor, in the LCA-mediated induction of both human and mouse CYP3As in vivo." @default.
- W2134065514 created "2016-06-24" @default.
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- W2134065514 date "2008-07-21" @default.
- W2134065514 modified "2023-09-23" @default.
- W2134065514 title "Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo" @default.
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- W2134065514 doi "https://doi.org/10.1124/dmd.108.021501" @default.
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