Uncovering a novel function of lysophospholipids through MS imaging technology

• Project/Area Number: 20K07047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kano Kuniyuki 東京大学, 大学院薬学系研究科(薬学部), 助教 (50636404)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 質量分析イメージング / リゾリン脂質 / リン脂質代謝 / MSイメージング / 誘導体化 / イメージングMS

Outline of Research at the Start

リゾホスファチジン酸やリゾホスファチジルセリンといったリゾリン脂質は、プロスタグランジンに次ぐ、次世代の脂質メディエーターとして着目されている。これらのリゾリン脂質はある特定の状況下において、局所的に産生され、近傍の受容体に認識されると想定されているが、それを実際に捉える研究はほとんどなされていない。そこで本研究では、これまで申請者が発達させてきたイメージング質量分析技術により、特定のリゾリン脂質が、いつ・どこで産生されるのかといった時空間的情報を得ることで、リゾリン脂質の新たな生理機能の解明を目的とする。

Outline of Final Research Achievements

This study focuses on the development of a highly sensitive mass spectrometry imaging method to visualize trace amounts of bioactive lysophospholipids. In addition, we aimed to analyze local fluctuations of lysophospholipids and elucidate their physiopathological functions. To achieve these goals, we successfully developed a novel mass spectrometry imaging method using Phos-tag derivatization. This technique enabled the visualization of trace amounts of lysophospholipids, including LPA and S1P. Using these mass spectrometry imaging methods, we further investigated the localization of lysophospholipids and revealed the LPA2-dependent suppression mechanism of sperm apoptosis as well as the LPA supply mechanism in hair follicle formation. In addition, we performed an in-depth analysis of various mouse models to investigate the accumulation of lysophospholipids under specific pathological conditions.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、生理活性リゾリン脂質（LPAおよびS1P）の局在が明確に可視化することが可能になったことで、これらの生理病理機能を解明するための基礎研究が加速することが期待される。また今後、本技術を様々なヒト病理検体に適用し、特定の病態におけるリゾリン脂質の局在変動を解明できれば、創薬やバイオマーカー探索に貢献できることが期待される。

Research Products

• [Int'l Joint Research] Boston Children's Hospital(米国)
• [Journal Article] Distributions of CHN compounds in meteorites record organic syntheses in the early solar system (2023)
  • Author(s): Furukawa Yoshihiro、Saigusa Daisuke、Kano Kuniyuki、Uruno Akira、Saito Ritsumi、Ito Motoo、Matsumoto Megumi、Aoki Junken、Yamamoto Masayuki、Nakamura Tomoki
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-023-33595-0
  • Peer Reviewed / Open Access
• [Journal Article] Direct activation of microglia by β-glucosylceramide causes phagoptosis of neurons that exacerbates Gaucher disease. (2023)
  • Author(s): Shimizu T, Schutt C R, Izumi Y, Tomiyasu N, Omahdi Z, Kano K, Takamatsu H, Aoki J, Bamba T, Kumanogoh A, Takao M, Yamasaki S*.
  • Journal Title: Immunity Volume: 56 Issue: 2 Pages: 1-13
  • DOI: 10.1016/j.immuni.2023.01.008
  • Peer Reviewed / Open Access
• [Journal Article] Persistent elevation of lysophosphatidylcholine promotes radiation brain necrosis with microglial recruitment by P2RX4 activation (2022)
  • Author(s): N Kondo, Y Sakurai, T Takata, K Kano, K Kume, M Maeda, N Takai, S Suzuki et al.,
  • Journal Title: scientific reports Volume: 12 Issue: 1 Pages: 8718-8718
  • DOI: 10.1038/s41598-022-12293-3
  • Peer Reviewed / Open Access
• [Journal Article] Changes in Lysophospholipid Components in Ulcerative Colitis and Colitis-associated Cancer (2022)
  • Author(s): SONODA HIROFUMI、KITAMURA CHIEKO、KANO KUNIYUKI、ANZAI HIROYUKI、NAGAI YUZO、ABE SHINYA、YOKOYAMA YUICHIRO、ISHII HIROAKI、KISHIKAWA JUNKO、MURONO KOJI、EMOTO SHIGENOBU、SASAKI KAZUHITO、KAWAI KAZUSHIGE、NOZAWA HIROAKI、AOKI JUNKEN、ISHIHARA SOICHIRO
  • Journal Title: Anticancer Research Volume: 42 Issue: 5 Pages: 2461-2468
  • DOI: 10.21873/anticanres.15724
  • Peer Reviewed
• [Journal Article] Lysophospholipid Mediators in Health and Disease (2022)
  • Author(s): Kano Kuniyuki、Aoki Junken、Hla Timothy
  • Journal Title: Annual Review of Pathology: Mechanisms of Disease Volume: 17 Issue: 1 Pages: 459-483
  • DOI: 10.1146/annurev-pathol-050420-025929
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine mediates fast decline in kidney function in diabetic kidney disease (2022)
  • Author(s): Yoshioka Kentaro、Hirakawa Yosuke、Kurano Makoto、Ube Yuko、Ono Yoko、Kojima Kensuke、Iwama Taiga、Kano Kuniyuki、Hasegawa Sho、Inoue Tsuyoshi、Shimada Takashi、Aoki Junken、Yatomi Yutaka、Nangaku Masaomi、Inagi Reiko
  • Journal Title: Kidney International Volume: 101 Issue: 3 Pages: 510-526
  • DOI: 10.1016/j.kint.2021.10.039
  • Peer Reviewed / Open Access
• [Journal Article] An ATX-LPA6-Gα13-ROCK axis shapes and maintains caudal vein plexus in Zebrafish (2021)
  • Author(s): Okasato R., Kano K., Kise R., Inoue A., Fukuhara S., Aoki J.
  • Journal Title: iScience Volume: 24 Issue: 11 Pages: 103254-103254
  • DOI: 10.1016/j.isci.2021.103254
  • Peer Reviewed
• [Journal Article] Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag (2021)
  • Author(s): Iwama Taiga、Kano Kuniyuki、Saigusa Daisuke、Ekroos Kim、van Echten-Deckert Gerhild、Vogt Johannes、Aoki Junken
  • Journal Title: Analytical Chemistry Volume: 93 Issue: 8 Pages: 3867-3875
  • DOI: 10.1021/acs.analchem.0c04479
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis (2021)
  • Author(s): Uranbileg Baasanjav、Ito Nobuko、Kurano Makoto、Kano Kuniyuki、Uchida Kanji、Sumitani Masahiko、Aoki Junken、Yatomi Yutaka
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 3984-3984
  • DOI: 10.1038/s41598-021-83569-3
  • Peer Reviewed / Open Access
• [Journal Article] Suppressing postcollection lysophosphatidic acid metabolism improves the precision of plasma LPA quantification (2021)
  • Author(s): Kano Kuniyuki、Matsumoto Hirotaka、Kono Nozomu、Kurano Makoto、Yatomi Yutaka、Aoki Junken
  • Journal Title: Journal of Lipid Research Volume: 62 Pages: 100029-100029
  • DOI: 10.1016/j.jlr.2021.100029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] リピドミクス分析のための 質量分析法の開発とその臨床応用 (2022)
  • Author(s): 可野 邦行
  • Organizer: BPCNPNPPP4 学会合同年会
  • Invited
• [Presentation] Visualization of Phospholipid Metabolism Based on MS Imaging Technology (2022)
  • Author(s): Kuniyuki Kano
  • Organizer: Gordon Research Conferences
  • Int'l Joint Research / Invited
• [Presentation] Development of Mass spectrometry techniques for peering deeper into the phospholipid diversity (2022)
  • Author(s): Kuniyuki Kano, Taiga Iwama, Junken Aoki
  • Organizer: 第95回 日本生化学会大会
  • Invited
• [Presentation] Development of an on-tissue derivatization method for MALDI mass spectrometry imaging of bioactive lipids containing phosphate monoester using Phos-tag (2021)
  • Author(s): Kuniyuki Kano
  • Organizer: 2021 AOCS Annual Meeting & Expo
  • Int'l Joint Research / Invited
• [Presentation] Phos-tag誘導体化法による新たな質量イメージング法の開発 (2021)
  • Author(s): 可野邦行
  • Organizer: 日本電気泳動学会 第72回総会
  • Invited
• [Presentation] リン脂質研究における新たな質量分析イメージング法の開発とその応用 (2021)
  • Author(s): 可野邦行、 岩間大河、 青木淳賢
  • Organizer: 第46回日本医用マススペクトル学会年会
  • Invited
• [Presentation] Novel MS Imaging Methods for Phospholipid Analysis (2021)
  • Author(s): Kuniyuki Kano
  • Organizer: 100 Minutes with ILS Imaging lipidomics
  • Int'l Joint Research / Invited
• [Presentation] リン脂質および脂質メディエーターの質量分析イメージング (2020)
  • Author(s): 可野 邦行、岩間 大河、青木 淳賢
  • Organizer: フォーラム2020：衛生薬学・環境トキシコロジー
  • Invited
• [Presentation] リゾホスファチジン酸はLPA2受容体を介して精子形成細胞のアポトーシスを抑制する (2020)
  • Author(s): 可野邦行、菅原拓海、青木淳賢
  • Organizer: 第62回日本脂質生化学会
• [Book] メタボロミクス実践ガイド (2021)
  • Author(s): 馬場 健史、平山 明由、松田 史生、津川 裕司
  • Total Pages: 334
  • Publisher: 羊土社
  • ISBN: 9784758122511
• [Book] 糖尿病学2020 (2020)
  • Author(s): 門脇 孝
  • Total Pages: 156
  • Publisher: 診断と治療社
  • ISBN: 9784787824639
• [Remarks] 東京大学薬学研究科衛生化学教室ホームページ
  • URL: https://sites.google.com/view/eiseikagaku-jp/