2016 Fiscal Year Final Research Report
Elucidation of the regulatory mechanism of lipid metabolism by intronic microRNA-33a, -33b
| Project/Area Number |
26461144
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 脂質代謝 / マイクロRNA / SREBP |
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| Outline of Final Research Achievements |
miR-33a is located in the intron of SREBP2, which is a main transcriptional factor that regulates cholesterol homeostasis. On the other hand, miR-33b is located in the intron of SREBP1, which regulates fatty acid homeostasis in human. To elucidate the function of miR-33a in various organs or cells, we developed miR-33a conditional KO mice. When miR-33a was ablated in fibroblast cells, cardiac fibrosis was inhibited under pressure-overload condition via modulation of lipid rafts. To elucidate the function of miR-33b in vivo, we developed miR-33b knock-in mice, which have human miR-33b sequence in the same intron of SREBP1 as human. These mice showed reduced expression of ABCA1 and decreased levels of serum HDL-C. These results indicate that miR-33a/b have multiple functions in regulating lipid homeostasis.
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| Free Research Field |
循環器内科学
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