2015 Fiscal Year Annual Research Report
脂質代謝を起点としたマイクロRNA、転写因子、エピゲノムの相互作用の解明
Publicly Offered Research
| Project Area | Crosstalk of transcriptional control and energy pathways by hub metabolites |
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| Project/Area Number |
26116716
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| Research Institution | Kyoto University |
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Principal Investigator |
尾野 亘 京都大学, 医学(系)研究科(研究院), 准教授 (00359275)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | マイクロRNA / 脂質代謝 / 転写因子 / エピゲノム |
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| Outline of Annual Research Achievements |
1. miR-33aおよび33bとその宿主遺伝子であるSrebp2、Srebp1の生体内での役割の解明:a) 栄養状態の変化による脂質恒常性に対する検討。miR-33bノックインマウスとmiR-33a欠損マウスの交配により、miR-33aおよびmiR-33bの有無による4種類のマウスを作製することができた。miR-33a欠損マウスにおいて最もHDLコレステロールが高く、miR-33bノックインマウスでは最もHDL-Cが低下した。また、糖・脂質の基質の流れについてメタボローム解析を行った。主成分分析において、miR-33a欠損マウス、miR-33bノックインマウス、コントロールマウスの分布が分かれ、さらにその原因追求している。また、miR-33aがラフトにおけるコレステロールを上昇させ、細胞増殖に働くことを明らかとした。b)骨髄機能の変化。マイクロRNA-33a欠損マウスでの末梢血では、炎症性のLy6Chigh monocyteが減少していた。一方、骨髄内では逆にLy6Chigh monocyteは増加していた。骨髄中では造血幹細胞のアポトーシスが減少し、Ly6Chigh monocyteの増加の原因と考えられた。一方、末梢でのLy6Chigh monocyteの減少は骨髄内の単球の末梢への移送が低下しているためと考えられた。
2.脂質代謝状態の変化におけるmiR-33/Set7/H3K4メチル化の影響の解析：miR-33aがSet7の発現制御を行っていることを明らかとした。さらに解析を続けている。
3.臓器別のmiR-33a/bの機能の解析：miR-33afloxマウス、miR-33bfloxマウスを作成し、臓器別のmiR-33a/bの解析を行った。心臓の線維化については線維芽細胞のmiR-33aが原因と考えられた。さらに肝臓、神経系での機能を解析中である。
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| Research Progress Status |
27年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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Research Products
(31 results)
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[Journal Article] Effects of Age and Sex on Clinical Outcomes after Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients with Triple Vessel Coronary Artery Disease.2015
Author(s)
Yamaji K, Shiomi H, Morimoto T, Nakatsuma K, Toyota T, Ono K, Furukawa Y, Nakagawa Y, Kadota K, Ando K, Shirai S, Onodera T, Watanabe H, Natsuaki M, Sakata R, Hanyu M, Nishiwaki N, Komiya T, Kimura T.
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Journal Title
Circulation.
Volume: 115
Pages: 020955
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery.2015
Author(s)
Miyamoto S, Usami S, Kuwabara Y, Horie T, Baba O, Hakuno D, Nakashima Y, Nishiga M, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Wang J, Ueyama K,Kimura T, Ono K.
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Journal Title
PLoS One.
Volume: 10
Pages: e0142904.
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] microRNA-33 regulates ApoE lipidation and Amyloid-β metabolism in the brain.2015
Author(s)
Kim J, Yoon H, Horie T, Burchett J, Restivo J, Rotllan N, Ramírez C, Verghese P, Ihara M, Hoe HS, Esau C, Fernández-Hernando C, Holtzman D, Cirrito J, Ono K, and Kim J.
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Journal Title
J Neurosci.
Volume: 35
Pages: 14717-26
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Influence of Sex on Long-Term Outcomes Afte Implantation of Bare-Metal Stent: A Multicenter Report From the Coronary Revascularization Demonstrating Outcome Study-Kyoto (CREDO-Kyoto) Registry Cohort-1.2015
Author(s)
Yamaji K, Shiomi H, Morimoto T, Toyota T, Ono K, Furukawa Y, Nakagawa Y, Kadota K, Ando K, Shirai S, Kato M, Takatsu Y, Doi O, Kambara H, Suwa S, Onodera T, Watanabe H, Natsuaki M, Kimura T
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Journal Title
Circulation.
Volume: 132
Pages: 2323-33
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Long-Term Outcomes After Coronary Stent Implantation in Patients Presenting With Versus Without Acute Myocardial Infarction (an Observation from Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2).2015
Author(s)
Yamaji K, Natsuaki M, Morimoto T, Ono K, Furukawa Y, Nakagawa Y, Kadota K, Ando K, Shirai S, Watanabe H, Shiomi H, Kimura T.
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Journal Title
Am J Cardiol.
Volume: 116
Pages: 15-23
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: A report from the CREDO-Kyoto registry cohort-2.2015
Author(s)
11:Izuhara M, Ono K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Tada T, Tazaki J, Horie T, Kuwabara Y, Baba O, Nishino T, Kita T, Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
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Journal Title
Atherosclerosis.
Volume: 242
Pages: 632-8
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] High-density Lipoprotein Cholesterol Levels and Cardiovascular Outcomes in Japanese Patients after Percutaneous Coronary Intervention from the CREDO-Kyoto Registry Cohort-2.2016
Author(s)
Masayasu Izuhara, Koh Ono, Hiroki Shiomi, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Satoshi Shizuta, Tomohisa Tada, Junichi Tazaki, Takahiro Horie, Yasuhide Kuwabara, Osamu Baba, Tomohiro Nishino, Toru Kita, Takeshi Kimura
Organizer
第80回日本循環器学会
Place of Presentation
仙台
Year and Date
2016-03-18 – 2016-03-20
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[Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Cardiac Myocytes.2016
Author(s)
Yasuhide Kuwabara, Koh Ono, Takahiro Horie, Shin Watanabe, Daihiko Hakuno, Yasuhiro Nakashima, Osamu Baba, Masayasu Izuhara, Masataka Nishiga, Shunsuke Usami, Tetsushi Nakao, Tomohiro Nishino, Yuya Ide, Fumiko Nakazeki, Satoshi Koyama, Toru Kita, Takeshi Kimura
Organizer
第80回日本循環器学会
Place of Presentation
仙台
Year and Date
2016-03-18 – 2016-03-20
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[Presentation] Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery.2016
Author(s)
Shunsuke Usami, Shoichi Miyamoto, Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Daihiko Hakuno, Yasuhiro Nakashima, Masataka Nishiga, Masayasu Izuhara, Tetsushi Nakao, Tomohiro Nishino, Yuya Ide, Fumiko Nakazeki, Koji Ueyama, Takeshi Kimura, Koh Ono
Organizer
第80回日本循環器学会
Place of Presentation
仙台
Year and Date
2016-03-18 – 2016-03-20
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[Presentation] Serum HDL cholesterol decreases in microRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor1 (Srebf1)2015
Author(s)
Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Nakashima Y, Hakuno D, Kimura T, Ono K.
Organizer
American Heart Association Annual Scientific Sessions 2015
Place of Presentation
Orlando, Florida
Year and Date
2015-11-07 – 2015-11-11
Int'l Joint Research
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[Presentation] High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: A report from the CREDO-Kyoto registry cohort-2.2015
Author(s)
Izuhara M, Ono K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Tada T, Tazaki J, Horie T, Kuwabara Y, Baba O, Nishino T, Kita T, Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2Investigators.
Organizer
American Heart Association Annual Scientific Sessions 2015
Place of Presentation
Orlando, Florida
Year and Date
2015-11-07 – 2015-11-11
Int'l Joint Research
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[Presentation] Kuwabara Y, Ono K, Horie T, Baba O, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Koyama S, Kita T, Kimura T2015
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