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Elucidation of molecular mechanism of novel lipid mediator, plasmalogen type lysophospholipid

Research Project

Project/Area Number 19H03372
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionThe University of Tokushima

Principal Investigator

YAMAMOTO Kei  徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 准教授 (30304504)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywordsリゾリン脂質 / 乾癬 / 脂質メディエーター / 慢性皮膚炎症疾患 / 褥瘡 / 表皮肥厚性疾患 / 皮膚バリア / プラズマローゲン / ホスホリパーゼ
Outline of Research at the Start

表皮は、体内の生命環境と非生命環境との間の境界バリアの役目を持ち体内からの水分の蒸発、体液の漏出あるいは病原体などの侵入から体を守っている。しかし、その代謝系の破綻は多岐に渡る皮膚疾患と関連する。我々はプラズマローゲン型リゾリン脂質が表皮肥厚性疾患を制御することを同定した。しかしこの新規リゾリン脂質が作動する分子機構および作用機序については充分に理解されていない。本研究ではプラズマローゲン型リゾリン脂質の分子機構を解明し、創薬および予防治療の開発に繋げていく。

Outline of Final Research Achievements

In this study, we demonstrated that plasmalogene-type lysophospholipids (P-LPE) are localized in the epidermal layer and are a target for drug discovery based on the alleviation of psoriasis. We also organically synthesized A-LPE(trans), a non-enzymatic metabolite of P-LPE, and showed that this lysophospholipid has potential as a wound healing agent by promoting the differentiation and migration of epidermal cells.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、表皮肥厚性疾患の発症要因に関する新しい概念の創成が期待され、皮膚炎症応答において新規脂質代謝系を明らかにした。また、基礎的な解析に加え、将来的に創薬開発も視野に入れており、本研究の成果を理論基盤とした創薬および予防治療の開発を展開したい。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

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

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Group IIA secreted phospholipase A2 controls skin carcinogenesis and psoriasis by shaping the gut microbiota2022

    • Author(s)
      Miki Yoshimi、Taketomi Yoshitaka、Kidoguchi Yuh、Yamamoto Kei、Muramatsu Kazuaki、Nishito Yasumasa、Park Jonguk、Hosomi Koji、Mizuguchi Kenji、Kunisawa Jun、Soga Tomoyoshi、Boilard Eric、B. Gowda Siddabasave Gowda、Ikeda Kazutaka、Arita Makoto、Murakami Makoto
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 2

    • DOI

      10.1172/jci.insight.152611

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma2022

    • Author(s)
      Kudo Kai、Miki Yoshimi、Carreras Joaquim、Nakayama Shunya、Nakamoto Yasushi、Ito Masatoshi、Nagashima Etsuko、Yamamoto Kei、Higuchi Hiroshi、Morita Shin-ya、Inoue Asuka、Aoki Junken、Ando Kiyoshi、Nakamura Naoya、Murakami Makoto、Kotani Ai
    • Journal Title

      Cell Metabolism

      Volume: 34 Issue: 4 Pages: 615-633

    • DOI

      10.1016/j.cmet.2022.02.011

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Red-kerneled rice proanthocyanidin inhibits arachidonate 5-lipoxygenase and decreases psoriasis-like skin inflammation2020

    • Author(s)
      Toda Keisuke、Tsukayama Izumi、Nagasaki Yuki、Konoike Yuka、Tamenobu Asako、Ganeko Natsuki、Ito Hideyuki、Kawakami Yuki、Takahashi Yoshitaka、Miki Yoshimi、Yamamoto Kei、Murakami Makoto、Suzuki-Yamamoto Toshiko
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: - Pages: 108307-108307

    • DOI

      10.1016/j.abb.2020.108307

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secreted phospholipase PLA2G2D contributes to metabolic health by mobilizing omega3 polyunsaturated fatty acids in WAT2020

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

      Cell Reports

      Volume: 31 Issue: 5 Pages: 107579-107579

    • DOI

      10.1016/j.celrep.2020.107579

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] リン脂質による表皮肥厚性疾患の病態制御2020

    • Author(s)
      山本圭
    • Journal Title

      The Lipid

      Volume: 31 Pages: 47-52

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 皮膚バリアを調節する新しい脂質メカニズム2020

    • Author(s)
      山本圭
    • Journal Title

      生物工学

      Volume: 98 Pages: 540-543

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] リゾリン脂質の新しい機能2020

    • Author(s)
      山本圭
    • Journal Title

      生化学

      Volume: 92 Pages: 658-665

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling.2019

    • Author(s)
      Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 116(41) Issue: 41 Pages: 20689-20699

    • DOI

      10.1073/pnas.1902958116

    • NAID

      120007132272

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular Ca2+-dependent formation of N-acyl-phosphatidylethanolamines by human cytosolic phospholipase A2ε2019

    • Author(s)
      Binte Mustafiz Smriti Sultana、Uyama Toru、Morito Katsuya、Takahashi Naoko、Kawai Katsuhisa、Hussain Zahir、Tsuboi Kazuhito、Araki Nobukazu、Yamamoto Kei、Tanaka Tamotsu、Ueda Natsuo
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1864 Issue: 12 Pages: 158515-158515

    • DOI

      10.1016/j.bbalip.2019.158515

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enzymatic Synthesis of 1‐Alkyl‐2‐hydroxy‐ sn‐glycero‐2,3‐cyclic‐phosphate Using a Novel Lysoplasmalogen‐Specific Phopholipase D2019

    • Author(s)
      Sakasegawa S, Taira S, Yamamoto K, Sugimori D.
    • Journal Title

      European Journal of Lipid Science and Technology

      Volume: 122 Issue: 2 Pages: 1900227-1900227

    • DOI

      10.1002/ejlt.201900227

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 生理活性脂質リゾプラズマローゲンの機能の解明2021

    • Author(s)
      山本圭
    • Organizer
      第63回日本脂質生化学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒトとウシの乳汁中脂質プロファイル比較2021

    • Author(s)
      長崎祐樹,川井恵梨佳,丸岡紗也,大角美穂,津嘉山泉,川上祐生,高橋吉孝,岡崎愉加,三木寿美,山本圭,村上誠,山本登志子.
    • Organizer
      第63回日本脂質生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 表皮角化細胞におけるリゾプラズマローゲンの機能解析2021

    • Author(s)
      谷口晴菜,犬伏穂南,天野智仁,福田朱里,箱井春香,山本圭
    • Organizer
      第61回日本生化学会中国・四国支部例会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アトピー性皮膚炎におけるsPLA2-IIF/P-LPE経路の機能解析.2021

    • Author(s)
      犬伏穂南, 天野智仁, 三木寿美, 村上誠, 山本圭
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 皮膚適応修復におけるsPLA2-IIF/P-LPEの機能解析2021

    • Author(s)
      福田朱里,谷口晴菜,犬伏穂南, 天野智仁, 三木寿美, 村上誠, 山本圭
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] N-アシル-ホスファチジルエタノールアミンの生成におけるcPLA2epsilonの細胞内基質の検討2020

    • Author(s)
      宇山徹,Smriti Sultana, Brinte Mustafiz,森戸克弥,高橋尚子,川合克久,Zahir Hussain,坪井一人,荒木伸一,山本圭,田中保,上田夏生.
    • Organizer
      第62回日本脂質生化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 角質脂質リゾプラズマローゲンは乾癬のバイオマーカーである.2020

    • Author(s)
      福田朱里,生越那々子,中谷碧,箱井春香,山本圭.
    • Organizer
      第61回日本生化学会中国・四国支部例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 皮膚におけるリゾプラズマローゲンの機能解析.2020

    • Author(s)
      犬伏穂南,東坂菜摘,箱井春香,山本圭.
    • Organizer
      第61回日本生化学会中国・四国支部例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 皮膚バリア機能におけるリゾプラズマローゲンの機能の解明.2020

    • Author(s)
      箱井春香,山本圭.
    • Organizer
      第93回日本生化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分泌性ホスホリパーゼA2はエクソソームのリン脂質を分解する.2020

    • Author(s)
      三木寿美,山本圭,工藤海,幸谷愛,武富芳隆,村上誠.
    • Organizer
      第93回日本生化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Group IIF phospholipase A2/lysophosplasmalogen axis is a novel drug target for epidermal-hyperplastic diseases.2019

    • Author(s)
      Yamamoto, K., Hakoi, H., Miki, Y., and Murakami, M.
    • Organizer
      60th International Conference on the Bioscience of Lipids.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The roles of lysoplasmalogen in three-dimensional keratinocyte culture system.2019

    • Author(s)
      Hakoi, H. and Yamamoto, K.
    • Organizer
      60th International Conference on the Bioscience of Lipids.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IIF型分泌性ホスホリパーゼA2/リゾプラズマローゲン経路は表皮肥厚性疾患の新規創薬ターゲットである.2019

    • Author(s)
      山本圭,箱井春香,三木寿美,村上誠.
    • Organizer
      第61回日本脂質生化学会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質メタボローム解析が紐解く新しい脂質代謝2019

    • Author(s)
      山本圭
    • Organizer
      第4回メタボローム解析シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規脂質メディエーター、プラズマローゲン型リゾリン脂質の分子機能.2019

    • Author(s)
      山本圭.
    • Organizer
      第92回日本生化学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 皮膚三次元培養システムを用いたリゾプラズマローゲンの機能の解明.2019

    • Author(s)
      箱井春香,山本圭.
    • Organizer
      第92回日本生化学会
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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