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Application of the pleiotropic effects of HDL, focusing on apolipoprotein M and sphingosine 1-phosphate

Research Project

Project/Area Number 20H03573
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionThe University of Tokyo

Principal Investigator

Kurano Makoto  東京大学, 医学部附属病院, 准教授 (60621745)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsスフィンゴシン1-リン酸 / アポ蛋白M / HDL / 臨床検査 / スフィンゴシン1-リン酸 / アポリポ蛋白M / スフィンゴシン1-リン酸 / 多面的効果
Outline of Research at the Start

HDLには、コレステロール引き抜き能の他、生体にとって有用な多面的効果があり、この多面的効果は、HDL上のアポ蛋白M(ApoM)に結合しているスフィンゴシン1-リン酸(S1P)によると考えられている。本研究では、「ApoM-S1Pを利用することにより、HDLの多面的効果を臨床医学に導入できるのではないか」、という概念の下に、基礎研究(動物、細胞実験)と臨床研究の統合的アプローチにより、ApoM-S1Pによる臓器機能保護作用の機序を解明するとともに、ApoMリコンビナントおよびApoM ELISAを用いて本研究成果を治療医学的、検査医学的応用することを目指す。

Outline of Final Research Achievements

HDL possesses various beneficial properties, which is called pleiotropic effect, as well as its capacity of promoting cholesterol efflux. These pleiotropic effects are attributed to sphingosine 1-phosphate (S1P), a potent lipid mediator, riding on HDL via apolipoprotein M (ApoM). In this research I have elucidated the possibility of therapeutic application of ApoM-S1P for various human diseases such as diabetic nephropathy, sepsis, and liver diseases and that of development of novel laboratory testing on the prognosis of these diseases.

Academic Significance and Societal Importance of the Research Achievements

動脈硬化性疾患以外に、HDLコレステロール濃度が予後と疫学的に関係があるとされる腎疾患、敗血症、糖尿病は、未だに治療法、検査法においてアンメットニーズが大きい分野である。本研究では、HDLのアポ蛋白M、スフィンゴシン1-リン酸がこれらの疾患に対して保護的な役割があることを示すことができた。この成果は、これらのアンメットニーズが大きい疾患に対する新しい治療法の開発や、これらの疾患の多彩な予後について予測することのできる検査法の開発につながるものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (38 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (14 results) (of which Invited: 6 results) Book (5 results) Remarks (1 results)

  • [Int'l Joint Research] マイアミ大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ミラノ大学(イタリア)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Apolipoprotein M/sphingosine 1-phosphate protects against diabetic nephropathy2023

    • Author(s)
      Kurano Makoto、Tsukamoto Kazuhisa、Shimizu Tomo、Hara Masumi、Yatomi Yutaka
    • Journal Title

      Translational Research

      Volume: 258 Pages: 16

    • DOI

      10.1016/j.trsl.2023.02.004

    • URL

      https://localhost/en/publications/de0723eb-aa0d-496c-95b1-a9181f6321dd

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulations of urinary lipid mediators in acute bladder cystitis2023

    • Author(s)
      Sugimoto Nao、Morita Yoshifumi、Sakai Eri、Yatomi Yutaka、Kurano Makoto
    • Journal Title

      Prostaglandins Other Lipid Mediators

      Volume: 164 Pages: 106690-106690

    • DOI

      10.1016/j.prostaglandins.2022.106690

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulations of bioactive lipids and their receptors in postmortem Alzheimer’s disease brains2022

    • Author(s)
      Kurano Makoto、Saito Yuko、Uranbileg Baasanjav、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Yatomi Yutaka
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 14 Pages: 1066578-1066594

    • DOI

      10.3389/fnagi.2022.1066578

    • URL

      https://localhost/en/publications/7e882018-3b56-4f31-8295-fceda13dfbe5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apolipoprotein D modulates lipid mediators and osteopontin in an anti-inflammatory direction2022

    • Author(s)
      Kurano Makoto、Tsukamoto Kazuhisa、Kamitsuji Shigeo、Kamatani Naoyuki、Hasegawa Koji、Hara Masumi、Ishikawa Toshio、Yatomi Yutaka、Teramoto Tamio
    • Journal Title

      Inflammation Research

      Volume: 72 Issue: 2 Pages: 263

    • DOI

      10.1007/s00011-022-01679-8

    • URL

      https://pure.teikyo.jp/en/publications/f4239d5c-4ba0-403e-8974-1489f36729e0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decrease in serum levels of autotaxin in COVID-19 patients2022

    • Author(s)
      Shimura Takuya、Kurano Makoto、Okamoto Koh、Jubishi Daisuke、Hashimoto Hideki、Kano Kuniyuki、Igarashi Koji、Shimamoto Satoshi、Aoki Junken、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      Annals of Medicine

      Volume: 54 Issue: 1 Pages: 3188-3199

    • DOI

      10.1080/07853890.2022.2143554

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries2022

    • Author(s)
      Kurano Makoto、Jubishi Daisuke、Okamoto Koh、Hashimoto Hideki、Sakai Eri、Morita Yoshifumi、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Harada Sohei、Okugawa Shu、Doi Kent、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      Journal of Biomedical Science

      Volume: 29 Issue: 1 Pages: 1069-1087

    • DOI

      10.1186/s12929-022-00880-5

    • URL

      https://pure.teikyo.jp/en/publications/9853f9b4-2c1e-4eb9-9308-57eeb7ee90d4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐192022

    • Author(s)
      Kurano Makoto、Okamoto Koh、Jubishi Daisuke、Hashimoto Hideki、Sakai Eri、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Harada Sohei、Okugawa Shu、Doi Kent、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      Clinical and Translational Medicine

      Volume: 12 Issue: 10

    • DOI

      10.1002/ctm2.1069

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sphingosine 1‐phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids2022

    • Author(s)
      Uranbileg Baasanjav、Kurano Makoto、Kano Kuniyuki、Sakai Eri、Arita Junichi、Hasegawa Kiyoshi、Nishikawa Takeshi、Ishihara Soichiro、Yamashita Hiroharu、Seto Yasuyuki、Ikeda Hitoshi、Aoki Junken、Yatomi Yutaka
    • Journal Title

      Clinical and Translational Medicine

      Volume: 12 Issue: 9

    • DOI

      10.1002/ctm2.1056

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Understanding modulations of lipid mediators in cancer using a murine model of carcinomatous peritonitis2022

    • Author(s)
      Kurano Makoto、Sakai Eri、Yatomi Yutaka
    • Journal Title

      Cancer Medicine

      Volume: 11 Issue: 18 Pages: 3491-3507

    • DOI

      10.1002/cam4.4699

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycation of HDL Polymerizes Apolipoprotein M and Attenuates Its Capacity to Bind to Sphingosine 1-Phosphate2021

    • Author(s)
      Kobayashi Tamaki、Kurano Makoto、Nanya Mai、Shimizu Tomo、Ohkawa Ryunosuke、Tozuka Minoru、Yatomi Yutaka
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 28 Issue: 7 Pages: 730-741

    • DOI

      10.5551/jat.55699

    • NAID

      130008060164

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2021-07-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of sphingosine 1-phosphate by hepatobiliary cholesterol handling2020

    • Author(s)
      Kurano Makoto、Tsukamoto Kazuhisa、Hara Masumi、Tsuneyama Koichi、Nishikawa Takako、Ikeda Hitoshi、Yatomi Yutaka
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 11 Pages: 14655

    • DOI

      10.1096/fj.202001397r

    • URL

      https://pure.teikyo.jp/en/publications/9857a91f-dc52-4c4c-85f3-508a75abf1e7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of sphingosine 1-phosphate lyase retards the liver regeneration in mice after partial hepatectomy2020

    • Author(s)
      Kageyama Yuko、Uranbileg Baasanjav、Kusumoto Yoshika、Sakai Eri、Ikeda Hitoshi、Kurano Makoto、Yatomi Yutaka
    • Journal Title

      Bioscience Reports

      Volume: 40 Issue: 7

    • DOI

      10.1042/bsr20200592

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Establishment of a Measurement System for Sphingolipids in the Cerebrospinal Fluid Based on Liquid Chromatography-Tandem Mass Spectrometry, and Its Application in the Diagnosis of Carcinomatous Meningitis2020

    • Author(s)
      Sakai Eri、Kurano Makoto、Morita Yoshifumi、Aoki Junken、Yatomi Yutaka
    • Journal Title

      The Journal of Applied Laboratory Medicine

      Volume: 5 Issue: 4 Pages: 656-670

    • DOI

      10.1093/jalm/jfaa022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urinary autotaxin concentrations are associated with kidney injury2020

    • Author(s)
      Morita Yoshifumi、Kurano Makoto、Morita Eriko、Shimamoto Satoshi、Igarashi Koji、Sawabe Motoji、Aoki Junken、Yatomi Yutaka
    • Journal Title

      Clinica Chimica Acta

      Volume: 509 Pages: 156-165

    • DOI

      10.1016/j.cca.2020.06.019

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism.2020

    • Author(s)
      Nakawatari K, Kurano M, Araki O, Nishikawa M, Shimamoto S, Igarashi K, Aoki J, Murakami M, Yatomi Y.
    • Journal Title

      Clin Chim Acta.

      Volume: 503 Pages: 99-106

    • DOI

      10.1016/j.cca.2020.01.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protection against insulin resistance by apolipoprotein M/sphingosine-1-phosphate2020

    • Author(s)
      Kurano M, Tsukamoto K, Shimizu T, Kassai H, Nakao K, Aiba A, Hara M, Yatomi Y.
    • Journal Title

      Diabetes

      Volume: 69 Issue: 5 Pages: 867

    • DOI

      10.2337/db19-0811

    • NAID

      40022523253

    • URL

      https://pure.teikyo.jp/en/publications/a3d6e058-c85d-4ca5-b6af-142fe379f161

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 質量分析計を用いた生理活性脂質の臨床検査への導入を目指して2022

    • Author(s)
      蔵野 信, 矢冨 裕
    • Organizer
      日本臨床検査専門医会 第1回年次大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Possible contribution of ApoM/S1P axis to the anti-thrombotic properties of HDL2022

    • Author(s)
      Makoto Kurano, Yutaka Yatomi
    • Organizer
      第44回日本血栓止血学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] アポ蛋白M-スフィンゴシン1-リン酸は、糖尿病性腎症に対して保護的作用を有する2022

    • Author(s)
      蔵野 信,矢冨 裕
    • Organizer
      第64回 日本脂質生化学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アポ蛋白M・スフィンゴシン1-リン酸に着目したHDLの多面的効果の解明と医療応用2022

    • Author(s)
      蔵野 信,矢冨 裕
    • Organizer
      第54回 日本動脈硬化学会総会・学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病剖検脳でのスフィンゴ脂質、グリセロリン脂質の変動2022

    • Author(s)
      蔵野 信,斎藤 裕子, 矢冨 裕
    • Organizer
      第47回 日本医用マススペクトル学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 尿中生理活性脂質測定系の医療応用を目指して2022

    • Author(s)
      蔵野 信
    • Organizer
      第7回 日本医用マススペクトル学会 東部会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 2型糖尿病患者におけるグリセロリゾリン脂質の変動とその意義についての検討2020

    • Author(s)
      蔵野 信、小林 玉宜、矢冨 裕
    • Organizer
      第117回 日本内科学会総会・講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アポ蛋白Mは抗NETosis作用を有する2020

    • Author(s)
      蔵野 信、西川 真子、矢冨 裕
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] スフィンゴシン1-リン酸によるHDLの多面的効果の医療応用を目指して(シンポジウム)2020

    • Author(s)
      蔵野 信、矢冨 裕
    • Organizer
      第63回 日本脂質生化学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 肝-胆汁間コレステロールハンドリングに伴うリゾリン脂質・セラミドの変動2020

    • Author(s)
      蔵野 信、塚本 和久、矢冨 裕
    • Organizer
      第63回 日本脂質生化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脂質メディエーターとしてのリン脂質とその関連物質(シンポジウム)2020

    • Author(s)
      蔵野 信、矢冨 裕
    • Organizer
      第52回日本動脈硬化学会総会・学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] リゾホスファチジルイノシトールは、催炎症リゾリン脂質メディエーターである2020

    • Author(s)
      蔵野 信、塚本 和久、矢冨 裕
    • Organizer
      第52回日本動脈硬化学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規催炎症リゾリン脂質リゾホスファチジルイノシトールの糖尿病の病態生理における役割の検討2020

    • Author(s)
      蔵野 信、矢冨 裕
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アポ蛋白Mは、シスプラチン腎症に対して保護的作用を持つ2020

    • Author(s)
      蔵野 信、森田 賢史、矢冨 裕
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Book] Medical Practice2023

    • Author(s)
      蔵野 信
    • Total Pages
      160
    • Publisher
      文光堂
    • Related Report
      2022 Annual Research Report
  • [Book] 臨床化学2022

    • Author(s)
      蔵野 信,矢冨 裕
    • Total Pages
      6
    • Publisher
      臨床化学会
    • Related Report
      2022 Annual Research Report
  • [Book] Medical Science Digest2022

    • Author(s)
      蔵野 信,矢冨 裕
    • Total Pages
      7
    • Publisher
      ニュー・サイエンス社
    • Related Report
      2022 Annual Research Report
  • [Book] ヒトサンプルを用いた生理活性脂質測定系によるヒト疾患病態の解明と臨床検査への応用2020

    • Author(s)
      蔵野信, 矢冨裕
    • Total Pages
      5
    • Publisher
      日本臨床検査医学会
    • Related Report
      2020 Annual Research Report
  • [Book] スフィンゴシン1-リン酸と動脈硬化2020

    • Author(s)
      蔵野信
    • Total Pages
      4
    • Publisher
      科学評論社
    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京大学医学部附属病院検査部

    • URL

      http://lab-tky.umin.jp/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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