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Elucidation of the regulatory mechanism of lipid metabolism by intronic microRNA-33a, -33b

Research Project

Project/Area Number 26461144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKyoto University

Principal Investigator

HORIE TAKAHIRO  京都大学, 医学研究科, 助教 (20565577)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脂質代謝 / マイクロRNA / SREBP / 動脈硬化
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.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (35 results)

All 2017 2016 2015 2014 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (20 results) (of which Int'l Joint Research: 2 results,  Invited: 4 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] 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] MSH2 Dysregulation Is Triggered by Proinflammatory Cytokine Stimulation and Is Associated with Liver Cancer Development.2016

    • Author(s)
      Eso Y, Takai A, Matsumoto T, Inuzuka T, Horie T, Ono K, Uemoto S, Lee K, Edelmann W, Chiba T, Marusawa H.
    • Journal Title

      Cancer Research

      Volume: 76 Issue: 15 Pages: 4383-93

    • DOI

      10.1158/0008-5472.can-15-2926

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Emerging Novel Biomarkers for Arteriosclerosis Obliterans2016

    • Author(s)
      Horie T, Kimura T, Ono K.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 23 Issue: 2 Pages: 171-172

    • DOI

      10.5551/jat.ED028

    • NAID

      130005122030

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2015 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain.2015

    • Author(s)
      Kim J, Yoon H, Horie T, Burchett JM, Restivo JL, Rotllan N, Ramírez CM, Verghese PB, Ihara M, Hoe HS, Esau C, Fernández-Hernando C, Holtzman DM, Cirrito JR, Ono K, Kim J.
    • Journal Title

      J Neurosci.

      Volume: 35(44) Issue: 44 Pages: 14717-26

    • DOI

      10.1523/jneurosci.2053-15.2015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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
      2015 Research-status Report 2014 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNAs and lipoprotein metabolism.2014

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

      J Atheroscler Thromb

      Volume: 21 Pages: 17-22

    • NAID

      130004845461

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiac-Specific Inhibition of Kinase Activity in Calcium/Calmodulin-Dependent Protein Kinase Kinase-β Leads to Accelerated Left Ventricular Remodeling and Heart Failure after Transverse Aortic Constriction in Mice2014

    • Author(s)
      Shin Watanabe, Takahiro Horie, Kazuya Nagao, Yasuhide Kuwabara, Osamu Baba, Hitoo Nishi, Naoya Sowa, Michiko Narazaki, Tetsuya Matsuda, Genzou Takemura, Hiromichi Wada, Koji Hasegawa, Takeshi Kimura, Koh Ono
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 9 Pages: e108201-e108201

    • DOI

      10.1371/journal.pone.0108201

    • NAID

      120005496630

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] MicroRNA-33 Promotes Cardiac Fibrosis Through Maintaining Cellular Lpid Contents.2016

    • Author(s)
      Nishiga M, Horie T, Kuwabara Y, Nakao K, Kimura T, Ono K.
    • Organizer
      第20回 日本心不全学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Overexpression of the LincRNA Regulated by Pressure-Overload Leads to Cardiomyocyte Hypertrophy.2016

    • Author(s)
      Kuwabara Y, Horie T, Baba O, Nishiga M, Nakao M, Nishino T, Nakazeki F, Koyama S, Kimura T, Ono K.
    • Organizer
      第20回 日本心不全学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Changes and Physiological Meanings of Serum microRNA during Therapeutic Course of Acute Heart Failure.2016

    • Author(s)
      Koyama S, Kuragaichi T, Sato Y, Kuwabara Y, Horie T, Baba O, Kimura T, Ono K.
    • Organizer
      第20回 日本心不全学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] マイクロRNAによるHDL代謝制御2016

    • Author(s)
      堀江貴裕
    • Organizer
      第48回 日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] マイクロRNA-33を介した新たな脂質代謝制御機構の解明2016

    • Author(s)
      堀江貴裕、西野共達、馬場理、桑原康秀、木村剛、尾野亘
    • Organizer
      第45回日本心脈管作動物質学会
    • Place of Presentation
      徳島
    • Year and Date
      2016-02-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Srebp1のイントロンに存在するmicroRNA-33bはHDLコレステロールを減少させる2015

    • Author(s)
      堀江貴裕、西野共達、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、曽和尚也、矢作直也、島野仁、横出正之、北徹、木村剛、尾野亘
    • Organizer
      第23回日本血管生物医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Serum HDL Cholesterol decreases in microRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1).2015

    • Author(s)
      Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Naoya Sowa, Yasuhiro Nakashima, Daihiko Hakuno, Takeshi Kimura, Koh Ono
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serum HDL-C decreases in microRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1).2015

    • Author(s)
      Takahiro Horie, Tomohiro Nishino, Yasuhide Kuwabara, Osamu Baba, Takeshi Kimura, Koh Ono
    • Organizer
      Basic Cardiovascular Sciences Scientific Sessions 2015
    • Place of Presentation
      New Orleans, LA
    • Year and Date
      2015-07-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Srebf1のイントロンにmicroRNA-33bをノックインしたマウスはHDLコレステロールの減少を示す2015

    • Author(s)
      堀江貴裕、西野共達、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、曽和尚也、矢作直也、島野仁、横出正之、北徹、木村剛、尾野亘
    • Organizer
      第47回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Srebp1のイントロンに存在するmicroRNA-33bはHDLコレステロールを減少させる2015

    • Author(s)
      堀江貴裕、西野共達、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、曽和尚也、矢作直也、島野仁、横出正之、北徹、木村剛、尾野亘
    • Organizer
      第1回国際心血管薬物療法学会日本部会
    • Place of Presentation
      京都
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Srebf1のイントロンにmicroRNA-33bをノックインしたマウスはHDLコレステロールの減少を示す。2015

    • Author(s)
      堀江貴裕、西野共達、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、曽和尚也、矢作直也、島野仁、横出正之、北徹、木村剛、尾野亘
    • Organizer
      若手ワークショップ@伊香保(転写研究会&転写サイクル&転写代謝システム共催)
    • Place of Presentation
      群馬
    • Year and Date
      2015-02-05 – 2015-02-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 心血管代謝疾患形成に関与するマイクロRNAの機能解析2014

    • Author(s)
      堀江貴裕
    • Organizer
      第50回高血圧モデル学会学術総会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Srebf1のイントロンにmicroRNA-33bをノックインしたマウスはHDLコレステロールの減少を示す。2014

    • Author(s)
      堀江貴裕、西野共達、馬場理、桑原康秀、中尾哲史、西賀雅隆、宇佐美俊輔、出原正康、井手裕也、中関典子、小山智史、曽和尚也、木村剛、尾野亘
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 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)
      Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Masayuki Yokode, Takeshi Kimura, and Koh Ono
    • Organizer
      American Heart Association 2014 Scientific Sessions
    • Place of Presentation
      USA, Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Serum HDL-C decreases in microRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor (Srebf1).2014

    • Author(s)
      Takahiro Horie, Tomohiro, Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Takeshi Kimura, Koh Ono
    • Organizer
      9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress (MSDA)
    • Place of Presentation
      Japan, Kyoto
    • Year and Date
      2014-09-12 – 2014-09-14
    • Related Report
      2014 Research-status Report
  • [Presentation] MicroRNA-33 deficiency leads to high fat diet- induced obesity and insulin resistance in vivo.2014

    • Author(s)
      Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Takeshi Kimura, and Koh Ono
    • Organizer
      European Society of Cardiology Congress 2014
    • Place of Presentation
      Spain, Barcelona
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Research-status Report
  • [Presentation] マイクロRNA-33による脂質代謝制御機構の解明2014

    • Author(s)
      堀江貴裕
    • Organizer
      第46回 日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] SREBP-2のイントロンに存在するマイクロRNA-33はSREBP-1の発現を制御する。2014

    • Author(s)
      堀江貴裕
    • Organizer
      Research PlaNet 2014
    • Place of Presentation
      東京
    • Year and Date
      2014-05-10 – 2014-05-11
    • Related Report
      2014 Research-status Report
  • [Presentation] MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates Srebp1 in vivo.2014

    • Author(s)
      Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Naoya Yahagi, Hitoshi Shimano, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura, Koh Ono
    • Organizer
      The 18th International Vascular Biology Meeting (IVBM)
    • Place of Presentation
      Japan, Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] SREBP-2のイントロンに存在するマイクロRNA-33はSREBP-1の発現を制御する。2014

    • Author(s)
      堀江貴裕、西野共達、馬場理、桑原康秀、矢作直也、島野仁、横出正之、北徹、木村剛、尾野亘
    • Organizer
      第51回日本臨床分子医学会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-11 – 2014-04-12
    • Related Report
      2014 Research-status Report
  • [Remarks] 京都大学循環器内科 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 Research-status 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
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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