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マイクロRNA-33a/bとそのパッセンジャー鎖による代謝調節機構の解明

Research Project

Project/Area Number 14J05148
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Cardiovascular medicine
Research InstitutionKyoto University

Principal Investigator

西野 共達  京都大学, 医学研究科, 特別研究員(PD)

Project Period (FY) 2014-04-25 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2014: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsマイクロRNA / 脂質代謝 / コレステロール / 動脈硬化 / 核酸医療 / HDL-コレステロール
Outline of Annual Research Achievements

1) miR-33bと動脈硬化: miR-33b+/+Apoe-/-マウスでは、miR-33b-/-Apoe-/-マウスと比べて、血清HDL-C値の低下を認め、動脈硬化巣の増大と質的悪化を認めた。またこれまでmiR-33a欠損マウスでは認められなかったリポ蛋白代謝の変化を認めた。
2) miR-33欠損マウスとmiR-33bノックインマウスの交配: miR-33a-/-miR-33b-/-マウス(miR-33欠損マウス)、miR-33a+/+miR-33b-/-マウス(野生型)、miR-33a-/-miR-33b+/+マウス(ノックインノックアウトマウス)、miR-33a+/+miR-33b+/+マウス(miR-33bノックインマウス、ヒト化マウス)の四系統のマウスの樹立し、血清脂質プロファイル等のデータを収集した。結果、臓器・組織特異的にmiR-33a, miR-33bの発現レベルに違いがあることが明らかとなった。一例として、肝臓においてはmiR-33bがmiR-33aよりも多く発現し、血清HDL-C値に与える影響がより大きいことが明らかとなった。これらは今後の臓器・組織特異的なmiR-33a/b抑制治療を見据えた上での重要なデータとなる。
3) 臓器特異的miR-33a欠損マウスを用いた検討: miR-33aflox/floxマウスを樹立し、肝臓特異的miR-33a欠損マウスを確立した。全身ノックアウトマウスと同様に血清HDL-C値が上昇することが確認した。今後全身ノックアウトマウスで確認された表現型との関連について研究を進める。また、線維芽細胞特異的miR-33aノックアウト(Periostin-Cre)を用い、心臓線維芽細胞におけるコレステロール代謝が、心不全モデルにおける線維化に関わることが明らかとした(Nishiga M et al, Circ Res 2016)。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model.2017

    • Author(s)
      Izuhara M, Kuwabara Y, Saito N, Yamamoto E, Hakuno D, Nakashima Y, Horie T, Baba O, Nishiga M, Nakao T, Nishino T, Nakazeki F, Ide Y, Kimura M, Kimura T, Ono K.
    • Journal Title

      PLoS One

      Volume: 12(3) Issue: 3 Pages: e0172798-e0172798

    • DOI

      10.1371/journal.pone.0172798

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic changes of serum microRNA-122-5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation.2017

    • Author(s)
      Satoshi Koyama, Takashi Kuragaichi, Yukihito Sato, Yasuhide Kuwabara, Shunsuke Usami, Takahiro Horie, Osamu Baba, Daihiko Hakuno, Yasuhiro Nakashima, Tomohiro Nishino, Masataka Nishiga, Tetsushi Nakao, Hidenori Arai, Takeshi Kimura, Koh Ono
    • Journal Title

      ESC Heart Failure

      Volume: 4 Issue: 2 Pages: 112-121

    • DOI

      10.1002/ehf2.12123

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol.2016

    • Author(s)
      Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K.
    • Journal Title

      Circ Res.

      Volume: - Issue: 5 Pages: 835-847

    • DOI

      10.1161/circresaha.116.309528

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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)
      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.
    • Journal Title

      Atherosclerosis.

      Volume: 242(2) Issue: 2 Pages: 632-8

    • DOI

      10.1016/j.atherosclerosis.2015.05.010

    • NAID

      120005678183

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNAs and High-Density Lipoprotein Cholesterol Metabolism2015

    • Author(s)
      Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Kimura T.
    • Journal Title

      International Heart Journal

      Volume: 56 Issue: 4 Pages: 365-371

    • DOI

      10.1536/ihj.15-019

    • NAID

      130005087574

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      PLoS One.

      Volume: 10(11) Issue: 11 Pages: e0142904-e0142904

    • DOI

      10.1371/journal.pone.0142904

    • NAID

      120005749912

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-33a/b in Lipid Metabolism2015

    • Author(s)
      Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 2 Pages: 278-284

    • DOI

      10.1253/circj.CJ-14-1252

    • NAID

      130004927073

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway.2015

    • Author(s)
      Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Otsu K, Kita T, Kimura T, Ono K.
    • Journal Title

      Circulation Research

      Volume: 116 Issue: 2 Pages: 279-288

    • DOI

      10.1161/circresaha.116.304707

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interpapillary muscle distance independently affects severity of functional mitral regurgitation in patients with systolic left ventricular dysfunction.2014

    • Author(s)
      Kim K, Kaji S, An Y, Nishino T, Tani T, Kitai T, Furukawa Y.
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: 148 Issue: 2 Pages: 434-440

    • DOI

      10.1016/j.jtcvs.2013.09.029

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.2014

    • 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, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 5312-5312

    • DOI

      10.1038/srep05312

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice2017

    • Author(s)
      Nishino T, Horie T, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kimura T and Ono K
    • Organizer
      Keystone Symposium RNA-Based Approaches in Cardiovascular Diseases
    • Place of Presentation
      Keystone, CO, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice2017

    • Author(s)
      Nishino T, Horie T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kimura T and Ono K
    • Organizer
      第81回日本循環器学会総会学術集会
    • Place of Presentation
      金沢、日本
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNA-33bは動脈硬化形成を促進させる2016

    • Author(s)
      西野共達、堀江貴裕、馬場理、桑原康秀、中尾哲史、西賀雅隆、宇佐美俊輔、出原正康、中関典子、井手裕也、小山智史、木村剛、尾野亘
    • Organizer
      第48回日本動脈硬化学会総会
    • Place of Presentation
      東京、日本
    • Year and Date
      2016-07-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] MicroRNA-33b promotes formation of vulnerable atherosclerotic plaque2016

    • Author(s)
      Tomohiro Nishino
    • Organizer
      新学術領域 転写体者システム若手ワークショップ
    • Place of Presentation
      山梨県
    • Year and Date
      2016-02-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in vivo2015

    • Author(s)
      Tomohiro Nishino, Takahiro Horie, Osamu Baba, Yasuhide Kuwabara, Koh Ono
    • Organizer
      新学術領域 転写代謝システム若手ワークショップ
    • Place of Presentation
      群馬
    • Year and Date
      2015-02-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNA-33, located within Srebf2 intron, regulate fatty acid synthesis via targeting SREBF-1 in vivo2014

    • Author(s)
      Tomohiro Nishino, Takahiro Horie, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Naoya Sowa Takeshi Kimura, Koh Ono
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Microrna-33, Located within Srebf2 Intron, Regulate Fatty Acid Synthesis Via Targeting SREBP-1 in vivo2014

    • Author(s)
      T. Nishino, T. Horie, O. Baba, Y. Kuwabara, T Nakao, M. Nishiga, S. Usami, M. Izuhara, Y. Ide, F. Nakazeki, S. Koyama, M. Yokode, T. Kita, T. Kimura, K. Ono
    • Organizer
      AHA Scientific Sessions 2014
    • Place of Presentation
      米国 シカゴ
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] microRNA-33, embedded in Srebf2 intron, regulate fatty acid synthesis through targeting SREBP-1 in vivo2014

    • Author(s)
      T. Nishino, T. Horie, O. Baba, Y. Kuwabara, T. Nakao, M. Nishiga, S. Usami, M. Izuhara, K. Ono
    • Organizer
      MSDA 2014: 9th Metabolic Syndrome, Type2 Diabetes and Atherosclerosis Congress
    • Place of Presentation
      京都
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNA-33a, embedded in Srebf2 gene, regulate lipogenetic pathway in vivo2014

    • Author(s)
      T. Nishino, T. Horie, O. Baba, Y. Kuwabara, T. Nakao, M. Nishiga, S. Usami, M. Izuhara, K. Ono
    • Organizer
      ESC CONGRESS 2014
    • Place of Presentation
      スペイン バルセロナ
    • Year and Date
      2014-09-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] microRNA-33は生体内でSREBP-1を介して脂肪酸合成を制御する2014

    • Author(s)
      西野共達
    • Organizer
      新学術領域 転写代謝システム班会議
    • Place of Presentation
      仙台
    • Year and Date
      2014-07-12
    • Related Report
      2014 Annual Research Report
  • [Remarks] 京都大学医学部附属病院 循環器内科

    • URL

      http://kyoto-u-cardio.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学医学部附属病院循環器内科 心血管疾患分子機構解明グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/metabolic/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report

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Published: 2015-01-22   Modified: 2024-03-26  

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