2014 Fiscal Year Final Research Report
Effects of changes in hepatic miRNA expression on drug metabolism
| Project/Area Number |
24659074
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Research Collaborator |
KIMURA Kento
ODA Yuki
SATO Yusuke
HARASHIMA Hideyoshi
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | マイクロRNA / 発現変動 / 個人差 / 転写後調節 / 薬物代謝酵素 / 薬物動態 |
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| Outline of Final Research Achievements |
We investigated the changes in miRNA expression by rifampicin, which modulates the expression of various genes related to drug metabolism and pharmacokinetics, in human hepatocytes, and evaluated the relationship with the gene expression changes. We found that the expression of 40 miRNAs and 165 genes were changed (> 2-fold) upon treatment with 10 uM rifampicin. The changes in expression of 16 mRNA/miRNA pairs were inversely associated, indicating that some mRNA expression altered by rifampicin may result from miRNA regulation.
Knockdown of miR-122 in liver resulted in significant decrease of midazolam and tolbutamide hydroxylase activities and significant increase of morphine glucuronosyltransferase activity in mouse. These results suggested that the changes in miRNA expression in liver affect cytochrome P450 and UDP-glucuronosyltransferase activities. In addition, we found that knockdown of miR-34a has a therapeutic or protecting potential for liver cirrhosis.
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| Free Research Field |
薬物代謝
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