肝臓中microRNAの発現変動が薬物代謝酵素活性に及ぼす影響

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Author: 中島, 美紀ほか

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Publication date: 2015-05-26

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Note (General)：: 金沢大学新学術創成研究機構ナノ生命科学研究所ヒト初代培養肝細胞にリファンピシンを処置することにより40種類のmiRNAの発現が2倍以上に変化し、それらが標的遺伝子の発現変化をもたらしている可能性が示された。マウスにmiRNAに対するアンチセンスオリゴを尾静注し、肝臓中の発現をノックダウンすると、薬物...

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Material Type: 文書・図像類
Title: 肝臓中microRNAの発現変動が薬物代謝酵素活性に及ぼす影響
Author/Editor: 中島, 美紀
Nakajima, Miki
Author Heading: 中島, 美紀
Nakajima, Miki
Publication Date: 2015-05-26
Publication Date (W3CDTF): 2015-05-26
Alternative Title: Effects of changes in hepatic miRNA expression on drug metabolism
Periodical title: 平成26(2014)年度科学研究費補助金挑戦的萌芽研究研究成果報告書 = 2014 Fiscal Year Final Research Report
No. or year of volume/issue: 2012-04-01 - 2015-03-31
Volume: 2012-04-01 - 2015-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: 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
Target Audience: 一般
Note (General): 金沢大学新学術創成研究機構ナノ生命科学研究所
ヒト初代培養肝細胞にリファンピシンを処置することにより40種類のmiRNAの発現が2倍以上に変化し、それらが標的遺伝子の発現変化をもたらしている可能性が示された。マウスにmiRNAに対するアンチセンスオリゴを尾静注し、肝臓中の発現をノックダウンすると、薬物代謝酵素活性が変化したことから、miRNAが薬物代謝能の制御に重要な役割を担っていることをin vivoで明らかにした。
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.
研究課題/領域番号:24659074, 研究期間(年度):2012-04-01 - 2015-03-31
DOI: 10.24517/00050837
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=70266162
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24659074/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-24659074/24659074seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA