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Evaluation of physiologocal roles of USP2 in energy metabolism by using cell-specific knockout models

Research Project

Project/Area Number 18K06035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionRakuno Gakuen University

Principal Investigator

Kitamura Hiroshi  酪農学園大学, 獣医学群, 教授 (80312403)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsユビキチン / マクロファージ / 精巣 / 視床下部 / 神経 / エネルギー代謝 / 骨格筋 / インスリン感受性 / 間脳視床下部 / USP2 / GM-CSF / インスリン / 運動精子 / 交感神経 / ノックアウトマウス / 組織選択的ノックアウトマウス / 筋損傷 / 2型糖尿病 / 遺伝子改変マウス / 筋芽細胞 / インスリン抵抗性 / USP
Outline of Final Research Achievements

Roles of ubiquitin-specific protease (USP)2 on energy metabolism was investigated using in vivo models. Myocyte-selective Usp2 knockout mice represented changes in insulin sensitivity after a high-fat fed obesity model compared with wild type mice. Myeloid-selective Usp2 knockout mice exhibited impairment of sperm motility via mitochondrial dysfunction. The defects in sperm motility of Usp2 knockout mice was account for aberrant production of GM-CSF by testicular macrophages. On the other hand, USP2 in ventromedial hypothalamic neurons mitigates accumulation of reactive oxygen and phosphorylation of AMPK. Consequently, hypothalamic USP2 maintains normal blood glucose level through maintenance of sympathetic activation. Collectively, USP2 seems to be a key regulatory molecule for energy metabolism at plural hierarchies

Academic Significance and Societal Importance of the Research Achievements

本研究は細胞や個体のエネルギーの産生や消費を調節する新たな酵素を見出したという内容である。私たちが注目したUSP2は、①1千万人以上の患者のいる2型糖尿病の主要な原因となるインスリン感受性を変化させる分子であること、②また糖尿病の素因となる正常時の血糖値の上昇を抑える分子であること、③さらには不妊治療や希少動物の保護、成績優良家畜の育種などに使用される凍結精子の活動を高める分子であることを個体レベルで明らかにした。USP2は酵素であることから活性の人為的調節が可能であり、エネルギー代謝に関連した種々の疾患の克服のための創薬標的となることを示唆する成果である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (28 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (12 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] Monash University(オーストリア)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Application of the colorimetric loop-mediated isothermal amplification (LAMP) technique for genotyping <i>Cre</i>-driver mice2022

    • Author(s)
      FUJIMOTO Masaki、KITAMURA Hiroshi
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 84 Issue: 4 Pages: 507-510

    • DOI

      10.1292/jvms.21-0658

    • NAID

      130008164660

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] USP2 in the ventromedial hypothalamus modifies blood glucose levels by controlling sympathetic nervous activation2022

    • Author(s)
      Hashimoto Mayuko、Fujimoto Masaki、Konno Kohtarou、Lee Ming Liang、Yamada Yui、Yamashita Koya、Toda Chitoku、Tomura Michio、Watanabe Masahiko、Inanami Osamu、Kitamura Hiroshi
    • Journal Title

      The Journal of Neuroscience

      Volume: - Issue: 23 Pages: 4607-4618

    • DOI

      10.1523/jneurosci.2504-21.2022

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes2021

    • Author(s)
      Kitamura Hiroshi、Hashimoto Mayuko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1209-1209

    • DOI

      10.3390/ijms22031209

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm2020

    • Author(s)
      Hashimoto Mayuko、Kimura Shunsuke、Kanno Chihiro、Yanagawa Yojiro、Watanabe Takafumi、Okabe Jun、Takahashi Eiki、Nagano Masashi、Kitamura Hiroshi
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 78 Issue: 6 Pages: 2929-2948

    • DOI

      10.1007/s00018-020-03683-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lipin-2 degradation elicits a proinflammatory gene signature in macrophages2020

    • Author(s)
      Watahiki Asami、Shimizu Kouhei、Hoshikawa Seira、Chiba Mitsuki、Kitamura Hiroshi、Egusa Hiroshi、Fukumoto Satoshi、Inuzuka Hiroyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524 Issue: 2 Pages: 477-483

    • DOI

      10.1016/j.bbrc.2020.01.119

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Introduction of a plasmid and a protein into bovine and swine cells by water-in-oil droplet electroporation2020

    • Author(s)
      ISHINO Takeshi、KURITA Hirofumi、KIRISAWA Rikio、SHIMAMOTO Yoshinori、NUMANO Rika、KITAMURA Hiroshi
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 82 Issue: 1 Pages: 14-22

    • DOI

      10.1292/jvms.19-0475

    • NAID

      130007783759

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of ubiquitin‐specific protease 2 causes accumulation of reactive oxygen species, mitochondria dysfunction, and intracellular ATP decrement in C2C12 myoblasts2019

    • Author(s)
      Hashimoto Mayuko、Saito Natsuko、Ohta Haru、Yamamoto Kumiko、Tashiro Asuka、Nakazawa Kosuke、Inanami Osamu、Kitamura Hiroshi
    • Journal Title

      Physiological Reports

      Volume: 7 Issue: 14 Pages: 1-14

    • DOI

      10.14814/phy2.14193

    • NAID

      120006901082

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models2019

    • Author(s)
      Hiroshi Kitamura
    • Journal Title

      Molecules

      Volume: 24 Issue: 23 Pages: 4394-4394

    • DOI

      10.3390/molecules24234394

    • NAID

      120006901081

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation2018

    • Author(s)
      Kikuchi Kenta、Iida Mayumi、Ikeda Naoki、Moriyama Shigetaka、Hamada Michito、Takahashi Satoru、Kitamura Hiroshi、Watanabe Takashi、Hasegawa Yoshinori、Hase Koji、Fukuhara Takeshi、Sato Hideyo、Kobayashi Eri H.、Suzuki Takafumi、Yamamoto Masayuki、Tanaka Masato、Asano Kenichi
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 2 Pages: 635-651

    • DOI

      10.4049/jimmunol.1800040

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro2018

    • Author(s)
      Kitamura Hiroshi、Saito Natsuko、Fujimoto Junpei、Nakashima Ken-ichi、Fujikura Daisuke
    • Journal Title

      BMC Complementary and Alternative Medicine

      Volume: 18 Issue: 1 Pages: 138-138

    • DOI

      10.1186/s12906-018-2198-5

    • NAID

      120006798131

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>Establishment of protocol for preparation of gene-edited bovine ear-derived fibroblasts for somatic cell nuclear </b><b>transplantation </b>2018

    • Author(s)
      Takeshi Ishino, Mayuko Hashimoto, Misato Amagasa, Natsuko Saito, Osamu Dochi, Rikio Kirisawa, Hiroshi Kitamura
    • Journal Title

      Biomedical Research

      Volume: 39 Issue: 2 Pages: 95-104

    • DOI

      10.2220/biomedres.39.95

    • NAID

      130006708564

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and validation of novel anti-bovine CD163 monoclonal antibodies ABM-1A9 and ABM-2D62018

    • Author(s)
      Yoshinori Shimamoto, Junko Nio-Kobayashi, Hiroshi Watarai, Masashi Nagano, Natsuko Saito, Eiki Takahashi, Hidetoshi Higuchi, Atsushi Kobayashi, Takashi Kimura, Hiroshi Kitamura
    • Journal Title

      Veterinary Immunology and Immunopathology

      Volume: 198 Pages: 6-13

    • DOI

      10.1016/j.vetimm.2018.02.004

    • NAID

      120006798133

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 精巣マクロファージに発現するUSP2による精子運動機能の制御2022

    • Author(s)
      北村 浩、橋本茉由子、木村俊介、渡邊敬文、高橋英機、永野昌志
    • Organizer
      第29回日本病態生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マクロファージのユビキチンプロテアーゼ2が凍結精子の機能に与える役割2021

    • Author(s)
      橋本茉由子、木村俊介、菅野智裕、柳川洋二郎、渡邉敬文、高橋英機、永野昌志、北村 浩
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 精巣マクロファージのユビキチン特異的プロテアーゼ2が精子機能に与える影響2020

    • Author(s)
      橋本茉由子、木村俊介、菅野智裕、柳川洋二郎、渡邉敬文、岡部潤、高橋英機、永野昌志、北村 浩
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ユビキチン特異的プロテアーゼ2による筋芽細胞のミトコンドリアの機能維持と活性酸素の役割2019

    • Author(s)
      橋本茉由子、太田葉瑠、齊藤菜津子、山本久美子、稲波修、北村 浩
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 筋芽細胞におけるUSP2によるミトコンドリア機能制御2019

    • Author(s)
      太田葉瑠、橋本茉由子、齊藤奈津子、山本久美子、中澤康裕、稲波修、北村 浩
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Droplet-EP法による家畜細胞へのプラスミド・組前タンパク質の導入2019

    • Author(s)
      石野武志、栗田弘史、北村 浩
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新たなエネルギー代謝制御酵素USP2の視床下部での発現と機能2019

    • Author(s)
      橋本茉由子、今野幸太郎、渡辺雅彦、北村 浩
    • Organizer
      第24回グリアクラブ
    • Related Report
      2018 Research-status Report
  • [Presentation] 視床下部ユビキチン特異的プロテアーゼ2の発現と血糖調節に対する役割2018

    • Author(s)
      橋本茉由子、Lee Ming Liang、木村俊介、戸田知得、高橋英機、北村 浩
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] マクロファージに選択的なUsp2ノックアウトマウスの精巣機能の評価2018

    • Author(s)
      天笠美聡、菅野智裕、木村俊介、栁川洋二郎、岩永敏彦、高橋英機、永野昌志、北村 浩
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 視床下部ユビキチン特異的プロテアーゼ2の血糖値に対するフィードバック制御2018

    • Author(s)
      橋本茉由子、李 明亮、木村俊介、戸田知得、高橋英機、北村 浩
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] マクロファージ選択的ユビキチン特異的プロテアーゼ2欠損マウスの精巣機能の評価2018

    • Author(s)
      天笠美聡、菅野智裕、木村俊介、栁川洋二郎、岩永敏彦、高橋英機、永野昌志、北村 浩
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ユビキチン特異的プロテアーゼ2の視床下部における発現と血糖調節における役割2018

    • Author(s)
      橋本茉由子、Lee Ming Liang、木村俊介、戸田知得、高橋英機、北村 浩
    • Organizer
      第32回北海道薬物作用談話会
    • Related Report
      2018 Research-status Report
  • [Book] ゲノム編集食品~農林水産分野への応用と持続的社会の実現~第2編4章12021

    • Author(s)
      橋本茉由子、北村 浩
    • Total Pages
      7
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437169
    • Related Report
      2021 Annual Research Report
  • [Remarks] 酪農学園大学の北村浩教授らが活発な凍結精子を得るのに必要な酵素を発見

    • URL

      https://www.u-presscenter.jp/article/post-44651.html

    • Related Report
      2020 Research-status Report
  • [Remarks] https://www.facebook.com/RakunoGakuVetPhysiol/

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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