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Extracellular lipid metabolism and skin diseases

Research Project

Project/Area Number 16K18882
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionThe University of Tokyo (2017-2018)
Tokyo Metropolitan Institute of Medical Science (2016)

Principal Investigator

Miki Yoshimi  東京大学, 大学院医学系研究科(医学部), 特任研究員 (00632499)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsホスホリパーゼA2 / 脂質 / 皮膚疾患 / 癌 / 免疫 / 腸内細菌叢 / メタボローム / リポクオリティ / がん / 抗炎症 / 腸管 / 腸内フローラ
Outline of Final Research Achievements

sPLA2-IID resolves the harmful immune responses by controlling the levels of anti-inflammatory ω3 lipids. However, Pla2g2d-/- mice showed a marked attenuation of skin carcinogenesis. These results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.
While, sPLA2-IIA has been implicated in exacerbation of inflammation by producing lipid mediators and protection against infection by degrading bacterial membranes. We found that sPLA2-IIA deficiency ameliorated skin cancer. Metabolome analyses revealed that sPLA2-IIA affects intestinal microbiota. Thus, our results provide a new aspect of sPLA2-IIA as a regulator of intestinal commensal microbiota, and suggest that perturbation of this process is eventually associated with alterations of host responses in distal organs.

Academic Significance and Societal Importance of the Research Achievements

本研究は、炎症促進性脂質メディエーター動員酵素としてのPLA2の既成の概念とは異なる脂質代謝酵素の新しい動作原理を提示しており、炎症性疾患の制御および腸内細菌叢の研究領域に新しい概念を導入するものと言える。また、sPLA2-IIAによる腸内細菌とその代謝物の変化を定性的・定量的に捉えたことは、将来的に疾患の発症や予後を予測するための新規診断法の開発や当該代謝物を利用した創薬への応用展開が期待される。近年、ω3脂肪酸や腸内細菌叢の健康への効果が広く認識されつつあり、本研究成果は疾患の制御や予防において身近な概念として普及することが見込まれる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (36 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 6 results) Remarks (3 results)

  • [Int'l Joint Research] University of Washington(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] IPMC/CNRS/University of Nice(France)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Group IID, IIE, IIF and III secreted phospholipase A2s.2019

    • Author(s)
      Murakami M, Miki Y, Sato H, Murase R, Taketomi Y, Yamamoto K.
    • Journal Title

      Biochim Biophys Acta Mol Cell Biol Lipids.

      Volume: 1864 Issue: 6 Pages: 803-818

    • DOI

      10.1016/j.bbalip.2018.08.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preventive effect of <i>Dioscorea japonica</i> on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E<sub>2</sub> synthetic pathway2018

    • Author(s)
      Tsukayama I, Toda K, Takeda Y, Mega T, Tanaka M, Kawakami Y, Takahashi Y, Kimoto M, Yamamoto K, Miki Y, Murakami M, Suzuki-Yamamoto T.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 62 Issue: 2 Pages: 139-147

    • DOI

      10.3164/jcbn.17-54

    • NAID

      130006407477

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Group III phospholipase A2 promotes colitis and colorectal cancer2017

    • Author(s)
      Murase R, Taketomi Y, Miki Y, Nishito Y, Saito M, Fukami K, Yamamoto K, Murakami M.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12261-12261

    • DOI

      10.1038/s41598-017-12434-z

    • NAID

      120006535021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphatidylethanolamine dynamics are required for osteoclast fusion.2017

    • Author(s)
      Irie, A., Yamamoto, K., Miki, Y., and Murakami, M.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 46715-46715

    • DOI

      10.1038/srep46715

    • NAID

      120006534988

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] リン脂質代謝酵素によるリポクオリティ制御と炎症・免疫2017

    • Author(s)
      村上 誠、三木 寿美、山本 圭
    • Journal Title

      炎症と免疫

      Volume: 25 Pages: 290-297

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secreted Phospholipase A2 Specificity on Natural Membrane Phospholipids2017

    • Author(s)
      Yamamoto K, Miki Y, Sato H, Murase R, Taketomi Y, Murakami M
    • Journal Title

      Methods Enzymol

      Volume: 583 Pages: 101-117

    • DOI

      10.1016/bs.mie.2016.09.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual Roles of Group IID Phospholipase A2 in Inflammation and Cancer2016

    • Author(s)
      Miki Y, Kidoguchi Y, Sato M, Taketomi Y, Taya C, Muramatsu K, Gelb MH, Yamamoto K, Murakami M
    • Journal Title

      J Biol Chem

      Volume: 291(30) Issue: 30 Pages: 15588-601

    • DOI

      10.1074/jbc.m116.734624

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression and Function of Group IIE Phospholipase A2 in Mouse Skin2016

    • Author(s)
      Yamamoto K, Miki Y, Sato H, Nishito Y, Gelb MH, Taketomi Y, Murakami M
    • Journal Title

      J Biol Chem

      Volume: 291(30) Issue: 30 Pages: 15602-13

    • DOI

      10.1074/jbc.m116.734657

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Roles of the Secreted Phospholipase A2 Gene Family in Immunology2016

    • Author(s)
      Murakami M, Yamamoto K, Miki Y, Murase R, Sato H, Taketomi Y
    • Journal Title

      Adv Immunol

      Volume: 132 Pages: 91-134

    • DOI

      10.1016/bs.ai.2016.05.001

    • ISBN
      9780128047972
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 分泌性ホスホリパーゼA2とアレルギー疾患.2016

    • Author(s)
      村上誠, 三木寿美, 山本圭, 武富芳隆
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 65 Pages: 563-568

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] IIA型ホスホリパーゼA2は腸内細菌叢を制御する2018

    • Author(s)
      三木 寿美, 武富 芳隆, 山本 圭, 細見 晃司, 國澤 純, Siddabasave Gowda B. Gowda, 有田 誠, 村上 誠.
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Lipocalin-type prostaglandin D synthase as a potential biomarker of bovine mastitis2018

    • Author(s)
      Yuki Nagasaki, Erika Kawai, Mitsuki Tanaka, Keisuke Toda, Izumi Tsukayama, Yuki Kawakami, Yoshitaka Takahashi, Masumi Kimoto, Yuka Okazaki, Yoshimi Miki, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
    • Organizer
      59th International Conference on the Bioscience of Lipids
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] sPLA2分子群による皮膚疾患の制御2018

    • Author(s)
      三木 寿美, 山本 圭, 佐藤 弘泰, 武富 芳隆, 村上 誠.
    • Organizer
      文部科学省新学術領域研究「脂質クオリティが解き明かす生命現象」第4回領域会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] sPLA2分子群による皮膚疾患の制御2018

    • Author(s)
      三木 寿美.
    • Organizer
      公益財団法人小野医学研究財団第29回研究成果発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] III型分泌性ホスホリパーゼA2は動脈硬化の新規増悪因子である2018

    • Author(s)
      武富 芳隆, 佐藤 弘泰, 宮崎 拓郎, 三木 寿美, 山崎 文義, 瀬藤 光利, 村上 誠.
    • Organizer
      第60回日本脂質生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 白色脂肪細胞のベージュ化に関わるThermogenic sPLA2の同定2018

    • Author(s)
      佐藤 弘泰, 武富 芳隆, 三木 寿美, 村上 誠.
    • Organizer
      第60回日本脂質生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dual roles of group IID phospholipase A2 in inflammation and cancer.2017

    • Author(s)
      Yoshimi Miki, Yoshitaka Taketomi, Kei Yamamoto, Makoto Murakami.
    • Organizer
      15th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Group III phospholipase A2 is a novel promoting factor of colorectal diseases.2017

    • Author(s)
      Remi Murase, Yoshitaka Taketomi, Yoshimi Miki, Makoto Murakami.
    • Organizer
      15th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] An epidermal sPLA2 (PLA2G2F)/ plasmalogen-lysophosphatidylethanolamine axis is a novel drug target for epidermal-hyperplasic diseases.2017

    • Author(s)
      Kei Yamamoto, Shota Fujino, Yoshimi Miki, Makoto Murakami.
    • Organizer
      15th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] リピドミクスを応用した組織固有のsPLA2依存的脂質代謝経路の探索.2017

    • Author(s)
      三木 寿美, 山本 圭, 佐藤 弘泰, 村瀬 礼美, 武富 芳隆, 村上 誠.
    • Organizer
      第42回日本医用マスペクトル学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] LC-MS/MSを用いた表皮肥厚性疾患を制御する新規生理活性脂質の同定.2017

    • Author(s)
      山本 圭, 藤野 翔多, 三木 寿美, 村上 誠.
    • Organizer
      第42回日本医用マスペクトル学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] III型ホスホリパーゼA2は大腸疾患の促進因子である.2017

    • Author(s)
      村瀬 礼美, 武富 芳隆, 齋藤 萌, 三木 寿美, 佐藤 弘泰, 深見 希代子, 村上 誠.
    • Organizer
      第59回日本脂質生化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 破骨細胞における膜リン脂質の代謝動態:PEの合成・輸送・分解と膜融合.2017

    • Author(s)
      入江 敦, 山本 圭, 三木 寿美, 武富 芳隆, 村上 誠.
    • Organizer
      第59回日本脂質生化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Plasmalogen lysophosphatidylethanolamine is a novel regulator and biomarker for epidermal-hyperplasic diseases.2016

    • Author(s)
      Yamamoto, K., Miki, Y., Taketomi, Y., Murakami, M.
    • Organizer
      The 1st International Plasmalogen Symposium
    • Place of Presentation
      Kyushu University, Fukuoka
    • Year and Date
      2016-11-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] IID型分泌性ホスホリパーゼA2は皮膚免疫疾患を普遍的に抑制する.2016

    • Author(s)
      三木寿美, 城戸口優, 山本圭, 村上誠
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大学川内北キャンパス, 宮城県仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] IID型分泌性ホスホリパーゼA2は抗腫瘍免疫を抑制する.2016

    • Author(s)
      城戸口優, 山本圭, 三木寿美, 村上誠
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大学川内北キャンパス, 宮城県仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] IID型分泌性ホスホリパーゼA2はメタボリックシンドロームの新規抑制因子である.2016

    • Author(s)
      佐藤弘泰, 牛田絢子, 武富芳隆, 三木寿美, 村上誠
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大学川内北キャンパス, 宮城県仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 炎症および癌病態におけるIID型sPLA2の二面的役割.2016

    • Author(s)
      三木寿美, 城戸口優, 山本圭, 村上誠
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      にぎわい交流館AU, 秋田県秋田市
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 皮膚の恒常性と病態における二種のsPLA2の発現と機能.2016

    • Author(s)
      山本圭, 三木寿美, 佐藤弘泰, 武富芳隆, 村上誠
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      にぎわい交流館AU, 秋田県秋田市
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
  • [Presentation] マスト細胞を制御する第二のAnaphylactic sPLA2の同定.2016

    • Author(s)
      武富芳隆, 砂川アンナ, 入江敦, 山本圭, 三木寿美, 佐藤弘泰, 小林哲幸, 村上誠
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      にぎわい交流館AU, 秋田県秋田市
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
  • [Presentation] The two secreted phospholipase A2s PLA2G2F and PLA2G2E play distinct roles in skin homeostasis and diseases.2016

    • Author(s)
      Yamamoto, K., Miki, Y., Sato, H., Taketomi, Y., Lambeau, G., Gelb, M.H., Murakami, M.
    • Organizer
      The 7th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      La Jolla, USA
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東京大学大学院 医学研研究科 疾患生命工学センター 健康環境医工学部門(村上研究室)ホームページ

    • URL

      https://lmmhs.m.u-tokyo.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科・疾患生命工学センター・健康環境医工学部門(村上研)ホームページ

    • URL

      http://lmmhs.m.u-tokyo.ac.jp/

    • Related Report
      2017 Research-status Report
  • [Remarks] 東京都医学総合研究所 脂質代謝プロジェクト(村上研究室)

    • URL

      http://www.igakuken.or.jp/lipid/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-16  

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