Project/Area Number |
23390211
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Kyoto University |
Principal Investigator |
ONO KOH 京都大学, 医学(系)研究科(研究院), 講師 (00359275)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tomoyuki 関西医科大学, 医学部薬理学 (20362527)
|
Co-Investigator(Renkei-kenkyūsha) |
KAKEYA Hideaki 京都大学, 大学院・薬学研究科 (00270596)
SATO Fumiaki 京都大学, 大学院・薬学研究科 (20467426)
HORIE Takahiro 京都大学, 大学院・医学研究科循環器内科 (20565577)
|
Project Period (FY) |
2011-11-18 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
|
Keywords | マイクロRNA / HDL-C / 動脈硬化 / ABCA1 / SREBP-2 / SREBP-1 / 脂肪肝 / 動脈瘤 / 心肥大 |
Research Abstract |
MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, have indicated that miR-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high fat diet-induced obesity and liver steatosis. Using miR-33-/-Srebf1+/- mice we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33-/- mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.
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