• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucudating TGFbeta-BMP Signaling Disruption and Vascular Anomalies.

Research Project

Project/Area Number 20K07430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

Itoh Fumiko  東京薬科大学, 生命科学部, 准教授 (70502582)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsTGF-β / 血管新生 / がん転移 / がん悪液質 / BMP / ミオスタチン / 難治性血管疾患 / 遺伝子改変マウス / 肺高血圧 / 腫瘍転移 / 肺高血圧症 / 腫瘍血行性転移 / 動脈性肺高血圧症 / Myostatin / 筋肉
Outline of Research at the Start

TGF-βファミリーシグナルの異常は、難治性血管疾患の発症に関与している。しかし、血管病変が引き起こされるメカニズムは未解明であり、これら疾患の有効な治療法は存在しない。応募者は血管・リンパ管内皮細胞特異的TGF-β/BMPシグナル欠損マウスを解析し、これらマウスが難治性血管疾患モデルになりうる可能性を見出した。本研究では、マウスの生体血管において、TGF-β/BMPシグナルの均衡崩壊に起因する、血管病変のメカニズムおよび腫瘍血管に与える影響を明らかにし、難治性血管疾患治療薬および腫瘍血行性転移抑制薬の開発を目指す。

Outline of Final Research Achievements

The analysis of this genetically modified mice, which exhibits endothelial cell-specific BMP signaling deficiency, had the potential to provide valuable insights into the mechanism of pulmonary hypertension development and the development of therapeutic drugs. Furthermore, it has been revealed that TGF-β, which also acts as a factor in cancer progression, affects tumor vascular endothelial cells and lymphatic endothelial cells, promoting metastasis. Inhibiting TGF-β in endothelial cells is believed to contribute to the development of therapeutic drugs that can suppress cancer metastasis. Additionally, the development of a TGF-β family member, myostatin, inhibitory peptide has shown effective muscle-enhancing effects. Particularly, in cancer cachexia model mice, it showed that increasing food intake and preventing muscle wasting are crucial aspects of treatment.

Academic Significance and Societal Importance of the Research Achievements

肺動脈性肺高血圧症は予後不良の難病である。本研究で作成した遺伝子改変マウスは有望な肺高血圧症のモデルマウスと考えられ、今後の病態発症メカニズム解明や治療薬開発に役立つ可能性が高い。さらに、TGF-βシグナルは様々な側面で悪性的に働くことが示され、その阻害剤の開発は腫瘍転移抑制につながる可能性が高い。
開発したミオスタチン阻害ペプチド・MID-35はアナモレリンとの併用治療により食餌摂取量と筋肉消耗を効果的に改善できることを見出した。がん悪液質患者の治療において食事摂取量増加と筋肉消耗阻害が治療ポイントになると期待される。

Report

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

    (29 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Book (2 results)

  • [Int'l Joint Research] ベルギー/KU Leuven(ベルギー)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] KU Leuven(ベルギー)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] KU Leuven(ベルギー)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Combination Therapy with Anamorelin and a Myostatin Inhibitor is Advantageous for Cancer Cachexia in a Mouse Model2022

    • Author(s)
      Kako Hanada, Kunpei Fukasawa, Hiroki Hinata, Shu Imai, Kentaro Takayama, Hideyo Hirai, Rina Ohfusa, Yoshio Hayashi, Fumiko Itoh
    • Journal Title

      Cancer Sci

      Volume: 113 Issue: 10 Pages: 3547-3557

    • DOI

      10.1111/cas.15491

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transgenically expressed Helicobacter pylori CagA in vascular endothelial cells accelerates arteriosclerosis in mice.2022

    • Author(s)
      Tahmina K, Hikawa N, Takahashi-Kanemitsu A, Knight CT, Sato K, Itoh F, Hatakeyama M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 618 Pages: 79-85

    • DOI

      10.1016/j.bbrc.2022.06.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TGF-β signaling in lymphatic vascular vessel formation and maintenance2022

    • Author(s)
      Itoh Fumiko、Watabe Tetsuro
    • Journal Title

      Frontiers in Physiology

      Volume: 13 Pages: 1-7

    • DOI

      10.3389/fphys.2022.1081376

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelial-specific depletion of TGF-β signaling affects lymphatic function.2021

    • Author(s)
      Kunpei Fukasawa, Kako Hanada, Kei Ichikawa, Masanori Hirashima, Takahiro Takagi, Susumu Itoh, Testuro Watabe, Fumiko Itoh.
    • Journal Title

      Inflamm Regen .

      Volume: 41 Issue: 1 Pages: 35-35

    • DOI

      10.1186/s41232-021-00185-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice2021

    • Author(s)
      Ozawa T., Morikawa M., Morishita Y., Ogikubo K., Itoh F., Koinuma D., Nygren P.-A., Miyazono K.
    • Journal Title

      iScience

      Volume: 24 Issue: 5 Pages: 102488-102488

    • DOI

      10.1016/j.isci.2021.102488

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptide-2 from mouse myostatin precursor protein alleviates muscle wasting in cancer-associated cachexia2020

    • Author(s)
      Chiharu Ojima, Yuri Noguchi, Tatsuki Miyamoto, Yuki Saito, Hiroki Orihashi, Yasuhiro Yoshimatsu, Tetsuro Watabe, Kentaro Takayama, Yoshio Hayashi, Fumiko Itoh.
    • Journal Title

      Cancer Sci

      Volume: 111 Issue: 8 Pages: 2954-2964

    • DOI

      10.1111/cas.14520

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood and lymphatic systems are segregated by the FLCN tumor suppressor2020

    • Author(s)
      Tai-Nagara I, Hasumi Y, Kusumoto D, Hasumi H, Okabe K, Ando T, Matsuzaki F, Itoh F, Saya H, Liu C, Li W, Mukouyama Y, Linehan WM, Liu X, Hirashima M, Suzuki Y, Funasaki S, Satou Y, Furuya M, Baba M, Kubota Y.
    • Journal Title

      Nat. Commun.

      Volume: 11 Issue: 1 Pages: 6314-6314

    • DOI

      10.1038/s41467-020-20156-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 内皮細胞特異的 Dicer 欠損が腫瘍血管、生理的血管に与える影響2023

    • Author(s)
      深沢薫平、郷光希、平位秀世、伊東史子
    • Organizer
      第30回 日本血管生物医学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] TGF-βシグナルによるリンパ管内皮細胞制御2022

    • Author(s)
      伊東史子
    • Organizer
      第46回 日本リンパ学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TGF-β I型・II型受容体欠損が腫瘍血管・リンパ管に与える影響2022

    • Author(s)
      花田賀子、齋藤裕紀、平位秀世、伊東史子
    • Organizer
      第46回 日本リンパ学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Disruption of Endothelial TGF-β/BMP signal balance impairs vascular Homeostasis2022

    • Author(s)
      Fumiko Itoh
    • Organizer
      TGF-β meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BMP, but not TGF-β, signal is important for vascular homeostasis.2022

    • Author(s)
      Fumiko Itoh
    • Organizer
      13th BMP Conference 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Smad7+/-マウスを利用した血栓症モデルマウスの解析2022

    • Author(s)
      多川なつ美、高橋花音、平位秀世、伊東史子
    • Organizer
      第30回 日本血管生物医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 内皮細胞特異的 TGF-β I 型・II 型受容体欠損が腫瘍転移に与える影響2022

    • Author(s)
      花田賀子、齋藤裕紀、久保田義顕、平位秀世、伊東史子
    • Organizer
      第30回 日本血管生物医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TGF-β/BMP signal balance maintains vascular homeostasis.2021

    • Author(s)
      Fumiko Itoh
    • Organizer
      TGF-β Meeting in Uppsala.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] TGF-βシグナルが与えるリンパ管機能・恒常性維持への影響2021

    • Author(s)
      深沢勲平,花田賀子,市川圭,高木尊大,伊東進,平位秀世,伊東史子.
    • Organizer
      第29回 日本血管生物医学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Disruption of Endothelial TGF-β/BMP signal balance impairs vascular homeostasis.2021

    • Author(s)
      Fumiko Itoh
    • Organizer
      第44回 日本分子生物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 血管内皮細胞特異的TGF-βシグナルの欠損が血管に与える影響.2021

    • Author(s)
      花田賀子,齋藤裕紀,宮本樹,Murcus Fruttiger, 平位秀世,伊東史子.
    • Organizer
      第94回 日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] リンパ管機能維持におけるTGF-βシグナルの役割.2021

    • Author(s)
      伊東史子.
    • Organizer
      第94回 日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 腫瘍転移経路におけるTGF-βシグナルの役割.2021

    • Author(s)
      伊東史子.
    • Organizer
      第44回 日本リンパ学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 内細胞特異的TGF-βシグナルファミリー欠損がマウスリンパ管に与える影響2021

    • Author(s)
      伊東史子
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 腫瘍血管新生におけるTGF-βファミリーシグナルの役割2021

    • Author(s)
      伊東史子
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ミオスタチン阻害ペプチドを用いたがん悪液質改善効果2021

    • Author(s)
      日向 宏輝, 尾嶋 千遥, 野口 百合, 高山 健太郎, 林 良雄, 伊東 史子
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Depletion of Endothelial TGF-β Signaling Induces Tumor Angiogenesis and Metastasis2021

    • Author(s)
      Itoh F, Takagi T, Saito Y, Hanada K, Fruttiger M, Itoh S.
    • Organizer
      The 21st International Vascular Biology Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Book] 薬と生命を学ぶ人のための 基礎生化学2023

    • Author(s)
      伊東 進、宮澤 恵二、伊東 史子、奥脇 暢、高橋 勝彦、服部 光治、東 伸昭
    • Total Pages
      392
    • Publisher
      化学同人
    • ISBN
      9784759821666
    • Related Report
      2022 Annual Research Report
  • [Book] 血管・リンパ管の機能制御と疾患メカニズム2022

    • Author(s)
      伊東 史子、福原 茂朋
    • Total Pages
      244
    • Publisher
      化学同人
    • ISBN
      9784759817355
    • Related Report
      2022 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi