論文 - 詳細
| RRC ID | 56005 |
|---|---|
| 著者 | Sultana H, Watanabe K, Rana MM, Takashima R, Ohashi A, Komai M, Shirakawa H. |
| タイトル | Effects of Vitamin K₂ on the Expression of Genes Involved in Bile Acid Synthesis and Glucose Homeostasis in Mice with Humanized PXR. |
| ジャーナル | Nutrients |
| 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 (Abca3, Cyp2s1, Sult1b1), bile acid synthesis (Cyp7a1, Cyp8b1), and energy homeostasis (Aldoc, Slc2a5). Similar mRNA changes of CYP7A1 and CYP8B1 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. |
| 巻・号 | 10(8) |
| 公開日 | 2018-7-27 |
| DOI | 10.3390/nu10080982 |
| PII | nu10080982 |
| PMID | 30060524 |
| PMC | PMC6116188 |
| MeSH | ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism Animals Animals, Genetically Modified Bile Acids and Salts / biosynthesis* Bile Acids and Salts / genetics Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism Energy Metabolism / drug effects* Energy Metabolism / genetics Female Gene Expression / drug effects Glucose / metabolism* Glucose Transport Proteins, Facilitative / genetics Glucose Transport Proteins, Facilitative / metabolism Glucose Transporter Type 5 Hep G2 Cells Homeostasis Humans Lipid Metabolism / drug effects* Liver / drug effects* Liver / metabolism Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Mice Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Pregnane X Receptor Receptors, Steroid / metabolism* Sulfotransferases / metabolism Vitamin K 2 / analogs & derivatives* Vitamin K 2 / pharmacology Vitamins / pharmacology |
| IF | 4.171 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) |