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Elucidation of the molecular mechanism and regulation of T-cell senescence

Research Project

Project/Area Number 18H02812
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKeio University

Principal Investigator

SANO Motoaki  慶應義塾大学, 医学部(信濃町), 准教授 (30265798)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords炎症制御 / 線維化制御 / 心不全 / 慢性腎臓病 / 糖尿病 / 慢性炎症 / オステオポンチン / 免疫老化 / 線維化 / 糖尿病性腎臓病 / 肥満 / 老化 / 飽和脂肪酸 / T細胞
Outline of Final Research Achievements

Accumulation of fat in visceral adipose tissue causes chronic inflammation due to infiltration of immune cells, mainly macrophages. We have found that osteopontin secreted by senescent T cells is involved in chronic inflammation in visceral adipose tissue. In the present study, we found that removal of senescent T cells by targeting PD-1 (Programmed cell death protein 1) improves glucose metabolism. This method would also remove activated T cells, which is not desirable. Regulation of transcriptional activity of osteopontin is important as a therapeutic target. We have been trying to clarify the mechanism of activation and regulation of the transcriptional activity of osteopontin, which is observed not only in visceral obesity but also in myocardial infarction and diabetic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

肥満にともなうメタボリック症候群は、心筋梗塞、慢性腎臓病、心不全を引き起こし、健康長寿の妨げになる。これらの併存疾患の発症を予防するためには、肥満に伴う全身の炎症状態を軽減する必要がある。我々の研究は、オステオポンチンが心血管内分泌疾患発症を予測する、あるいは、治療効果を予測するバイオマーカーとして有用であることを明らかにしただけでなく、治療標的としても有望であることを明らかにした。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (25 results)

All 2020 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 10 results) Book (5 results)

  • [Journal Article] MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction2020

    • Author(s)
      Kohsuke Shirakawa, Jin Endo , Masaharu Kataoka, Yoshinori Katsumata, Atsushi Anzai, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Seien Ko, Shinichi Goto, Genki Ichihara, Keiichi Fukuda, Tohru Minamino, Motoaki Sano
    • Journal Title

      Journal of American Heart Association

      Volume: 9 Issue: 18

    • DOI

      10.1161/jaha.120.017071

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium-Glucose Co-Transporter 2 Inhibitors Correct Metabolic Maladaptation of Proximal Tubular Epithelial Cells in High-Glucose Conditions2020

    • Author(s)
      Shirakawa Kohsuke、Sano Motoaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 20 Pages: 7676-7676

    • DOI

      10.3390/ijms21207676

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Palmitate induces cardiomyocyte death via inositol requiring enzyme-1 (IRE1)-mediated signaling independent of X-box binding protein 1 (XBP1)2020

    • Author(s)
      Yamamoto Tsunehisa、Endo Jin、Kataoka Masaharu、Matsuhashi Tomohiro、Katsumata Yoshinori、Shirakawa Kohsuke、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Shimanaka Yuta、Kono Nozomu、Arai Hiroyuki、Shinmura Ken、Fukuda Keiichi、Sano Motoaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 526 Issue: 1 Pages: 122

    • DOI

      10.1016/j.bbrc.2020.03.027

    • URL

      https://pure.teikyo.jp/en/publications/ffcbfb02-ae99-471c-94d1-c41400c3176a

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] (Pro)renin receptor accelerates development of sarcopenia via activation of Wnt/YAP signaling axis2019

    • Author(s)
      Yoshida Naohiro、Endo Jin、Kinouchi Kenichiro、Kitakata Hiroki、Moriyama Hidenori、Kataoka Masaharu、Yamamoto Tsunehisa、Shirakawa Kohsuke、Morimoto Satoshi、Nishiyama Akira、Hashiguchi Akihiro、Higuchi Itsuro、Fukuda Keiichi、Ichihara Atsuhiro、Sano Motoaki
    • Journal Title

      Aging Cell

      Volume: 18 Issue: 5

    • DOI

      10.1111/acel.12991

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelial-Mesenchymal Transition Drives Expression of CD44 Variant and xCT in Pulmonary Hypertension2019

    • Author(s)
      Isobe Sarasa、Kataoka Masaharu、Endo Jin、Moriyama Hidenori、Okazaki Shogo、Tsuchihashi Kenji、Katsumata Yoshinori、Yamamoto Tsunehisa、Shirakawa Kohsuke、Yoshida Naohiro、Shimoda Masayuki、Chiba Tomohiro、Masuko Takashi、Hakamata Yoji、Kobayashi Eiji、Saya Hideyuki、Fukuda Keiichi、Sano Motoaki
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: Volume61,Issue3 Issue: 3 Pages: 367-379

    • DOI

      10.1165/rcmb.2018-0231oc

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of long term administration of tofogliflozin on chronic inflammation of visceral adipose tissue in mice with obesity induced by a high-fat diet2019

    • Author(s)
      Shirakawa Kohsuke、Yano Wataru、Inoue Keisuke、Katsumata Yoshinori、Endo Jin、Sano Motoaki
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0211387-e0211387

    • DOI

      10.1371/journal.pone.0211387

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction2018

    • Author(s)
      Yamamoto Tsunehisa、Endo Jin、Kataoka Masaharu、Matsuhashi Tomohiro、Katsumata Yoshinori、Shirakawa Kohsuke、Yoshida Naohiro、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Yamashita Kaoru、Nakanishi Hiroki、Shimanaka Yuta、Kono Nozomu、Shinmura Ken、Arai Hiroyuki、Fukuda Keiichi、Sano Motoaki
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 12 Pages: 0208396-0208396

    • DOI

      10.1371/journal.pone.0208396

    • URL

      https://localhost/en/publications/c494d8bc-a57b-4e2e-9922-c30bd4e08d67

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL (Interleukin)-10-STAT3-Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction2018

    • Author(s)
      Shirakawa Kohsuke、Endo Jin、Kataoka Masaharu、Katsumata Yoshinori、Yoshida Naohiro、Yamamoto Tsunehisa、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Kitakata Hiroki、Hiraide Takahiro、Fukuda Keiichi、Sano Motoaki
    • Journal Title

      Circulation

      Volume: 138 Issue: 18 Pages: 2021-2035

    • DOI

      10.1161/circulationaha.118.035047

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 全身のひずみを受け止める造血臓器機能の統合的理解2020

    • Author(s)
      佐野元昭
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 糖尿病細小および大血管障害と心不全の関係2020

    • Author(s)
      佐野元昭
    • Organizer
      第35回日本糖尿病合併症学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Obesity-related immune senescence and cardiomyopathy2019

    • Author(s)
      Motoaki Sano
    • Organizer
      Basic Cardiovascular Sciences
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 急性大動脈解離へ発症後の血管炎症のメカニズム2019

    • Author(s)
      佐野元昭
    • Organizer
      第60回日本脈管学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 睡眠障害が骨髄のマクロファージの分化・増殖のダイナミズムを修飾して動脈硬化を促進させる機序について2019

    • Author(s)
      佐野元昭
    • Organizer
      第29回日本循環薬理学会・第55回高血圧関連疾患モデル学会合同学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 非糖尿病専門医がすべき糖尿病診療2019

    • Author(s)
      佐野元昭
    • Organizer
      第67回日本心臓病学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨髄由来の単球がオステオポンチン産生マクロファージへと分化して心筋梗塞による創傷を治癒する機序2019

    • Author(s)
      佐野元昭
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 栄養エネルギー代謝から考える心不全2019

    • Author(s)
      佐野元昭
    • Organizer
      東京都内科医会 第32回医学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 肥満と心不全2019

    • Author(s)
      佐野元昭
    • Organizer
      第19回日本抗加齢医学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 代謝と分子機序を考慮した心血管病治療Cardiac Lipotoxicity2018

    • Author(s)
      佐野元昭
    • Organizer
      第22回 心不全学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脂質異常症と心臓病2018

    • Author(s)
      佐野元昭
    • Organizer
      第29回 炎症と循環器疾患研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 内臓脂肪型肥満による免疫老化の怖さ2018

    • Author(s)
      佐野元昭
    • Organizer
      第4回 Mets associated cancer 研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] Current Therapy 2020 Vol.38 No.42020

    • Author(s)
      佐野元昭
    • Total Pages
      94
    • Publisher
      ライフメディコム
    • Related Report
      2020 Annual Research Report
  • [Book] 月刊糖尿病 第121号2020

    • Author(s)
      佐野元昭
    • Total Pages
      96
    • Publisher
      医学出版
    • Related Report
      2020 Annual Research Report
  • [Book] アンチ・エイジング医学15巻5号2019

    • Author(s)
      新村健, 佐野元昭
    • Total Pages
      120
    • Publisher
      メディカルレビュー社
    • Related Report
      2019 Annual Research Report
  • [Book] Cutting Edge of Molecular Cardiology 新しい臨床を開拓するための分子循環器病学2019

    • Author(s)
      佐野元昭 山本恒久 遠藤仁
    • Total Pages
      210
    • Publisher
      南山堂
    • ISBN
      9784525249410
    • Related Report
      2018 Annual Research Report
  • [Book] 医学のあゆみ 心不全のすべて 分子生物学から緩和ケアまで:beyondガイドライン2018

    • Author(s)
      佐野元昭
    • Total Pages
      302
    • Publisher
      医歯薬出版
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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