Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Notes
A Novel Lithocholic Acid Derivative Upregulates Detoxification-Related Genes in Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids
Shigeru YamadaHiroyuki MasunoHiroyuki KagechikaAya TanataniYasunari Kanda
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2022 Volume 45 Issue 11 Pages 1720-1724

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Abstract

Vitamin D is a fat-soluble micronutrient that plays essential roles in a range of biological processes, including cell proliferation, inflammation, and metabolism. In this study, we investigated the effects of a novel synthetic lithocholic acid derivative with vitamin D activity (Dcha-20) on pharmacokinetic gene expression in human induced pluripotent stem cell-derived intestinal organoids. Compared with vitamin D3 treatment, Dcha-20 was found to upregulate the expression and enzyme activity of the drug-metabolizing enzyme CYP3A4, an indicator of intestinal functional maturation. In addition, Dcha-20 specifically increased expression levels of the xenobiotic detoxification enzyme UGT1A and excretion transporter MRP2. These results suggest that Dcha-20 promotes activity of the intrinsic defense system of the intestinal epithelium.

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© 2022 The Pharmaceutical Society of Japan
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