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- Title
Effects of Vitamin K2 on the Expression of Genes Involved in Bile Acid Synthesis and Glucose Homeostasis in Mice with Humanized PXR.
- Authors
Sultana, Halima; Watanabe, Kimika; Rana, Md Masud; Takashima, Rie; Ohashi, Ai; Komai, Michio; Shirakawa, Hitoshi
- Abstract
Pregnane X receptor (PXR) is a nuclear receptor activated by various compounds, including prescribed drugs and dietary ingredients. Ligand-specific activation of PXR alters drug metabolism and affects many other physiological conditions. Species-specific ligand preference is a considerable challenge for studies of PXR function. To increase translational value of the results of mouse studies, humanized mouse model expressing human PXR (hPXR) has been developed. Menaquinone-4 (MK-4), one of vitamin K2 analogs prescribed in osteoporosis, is a PXR ligand. We hypothesized that MK-4 could modulate the physiological conditions endogenously influenced by PXR, including those that have not been yet properly elucidated. In the present study, we investigated the effects of a single oral treatment with MK-4 on hepatic gene expression in wild-type and hPXR mice by using quantitative RT-PCR and DNA microarray. MK-4 administration altered mRNA levels of genes involved in drug metabolism (<italic>Abca3</italic>, <italic>Cyp2s1</italic>, <italic>Sult1b1</italic>), bile acid synthesis (<italic>Cyp7a1</italic>, <italic>Cyp8b1</italic>), and energy homeostasis (<italic>Aldoc</italic>, <italic>Slc2a5</italic>). Similar mRNA changes of <italic>CYP7A1</italic> and <italic>CYP8B1</italic> were observed in human hepatocarcinoma HepG2 cells treated with MK-4. These results suggest that MK-4 may modulate bile acid synthesis. To our knowledge, this is the first report showing the effect of MK-4 in hPXR mice.
- Subjects
ANIMAL experimentation; BLOOD sugar; EPITHELIAL cells; GENE expression; HOMEOSTASIS; MICE; ORAL drug administration; POLYMERASE chain reaction; VITAMIN K; REVERSE transcriptase polymerase chain reaction; OLIGONUCLEOTIDE arrays
- Publication
Nutrients, 2018, Vol 10, Issue 8, p982
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu10080982