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Detection of the activity of chronic inflammation in subcutaneous tissue by blood sampling and visualization of the process of tissue fibrosis

Research Project

Project/Area Number 20K09843
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionChiba University

Principal Investigator

AKITA SHINSUKE  千葉大学, 医学部附属病院, 講師 (00436403)

Co-Investigator(Kenkyū-buntansha) 木村 元子  千葉大学, 大学院医学研究院, 教授 (00345018)
三川 信之  千葉大学, 大学院医学研究院, 教授 (40595196)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsリンパ浮腫 / 線維化 / 静脈うっ滞 / ケロイド / リンパ管 / リンパ節 / 瘢痕 / 皮下組織 / 再疎通 / 鬱血 / Myosin light chain 9 / 血小板 / 慢性炎症
Outline of Research at the Start

本研究の目的は、採血によって皮膚皮下組織慢性炎症の活動性を客観化することと、線維化過程を可視化、治療することである。具体的には、血小板由来Myosin light chain 9(myl9)を介した炎症及び線維化の活動性の測定と、1000nmを超える波長領域を観察する近赤外線カメラによるリンパ組織の観察をコア技術として皮膚皮下組織炎症疾患の病態を解き明かす。第一のターゲットとしてリンパ浮腫発症過程における急性のリンパうっ滞から不可逆的組織変化へと至る病態を明らかにし、慢性リンパ浮腫予防治療の開発を進める。これと同時に、普遍的な皮膚や皮下組織の慢性炎症反応に伴う線維化の病理を明らかにする。

Outline of Final Research Achievements

The purpose of this study was to clarify the pathophysiology of fibrosis that occurs in the subcutaneous tissue and lymphatic system as a result of changes in lymphatic and venous stasis. In human subcutaneous tissue, fibrosis associated with lymphedema and scarring was observed as a typical fibrosis process. Since Myl9 levels in plasma were high in lymphedema with fibrosis after irradiation of human specimens, we tested this molecule in mouse models of lymphatic and venous stasis and demonstrated that activation of the CD69-Myl9 system is deeply involved in fibrosis in a congested tissue environment. In a congestive environment, the CD69-Myl9 system is activated in the subcutaneous tissue. In the congestive environment, leakage of blood cells from the subcutaneous tissue into the lymphatic vessels may contribute to fibrosis.

Academic Significance and Societal Importance of the Research Achievements

皮膚皮下組織の線維化については様々な病態を原因とするにもかかわらず炎症に基づく線維芽細胞の活性化として理解されてきた。本研究において明らかになった移植組織静脈うっ滞に伴うCD69-Myl9 systemの活性化とリンパ流の閉塞は、静脈のうっ滞とリンパ流のうっ滞の連動を示す新たな発見であり、今後の更なる病態の理解と治療方法の開発に貢献すると考えられる。リンパ浮腫並びに静脈うっ滞、その他皮下組織線維化に悩む人々にとって、より根治的な治療法の開発が進むことはquality of lifeの向上のために必要なことであり、本研究の成果は将来ヒトにおける診断や治療評価として社会実装できる可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2024 2023 2022 2021

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

  • [Journal Article] What are the key risk factors of keloid formation after repair of syndactyly of the toe?2023

    • Author(s)
      Tatsuya Ishigaki, Shinsuke Akita, Akikazu Udagawa, Hiroyuki Suzuki, Nobuyuki Mitsukawa
    • Journal Title

      J Orthop Sci .

      Volume: 23 Issue: 6 Pages: 00270-1

    • DOI

      10.1016/j.jos.2023.10.001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and Histological Effects of Partial Blood Flow Impairment in Vascularized Lymph Node Transfer2022

    • Author(s)
      Shinsuke Akita, Yuzuru Ikehara, Minami Arai, Hideki Tokumoto, Yoshihisa Yamaji, Kazuhiko Azuma, Yoshitaka Kubota, Hideaki Haneishi, Motoko Y Kimura, Nobuyuki Mitsukawa
    • Journal Title

      J Clin Med

      Volume: 11 Issue: 14 Pages: 4052-4052

    • DOI

      10.3390/jcm11144052

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Histological Changes in Lymphedema and Surgical Treatment Strategies2024

    • Author(s)
      Shinsuke Akita
    • Organizer
      The 10th World Symposium for Lymphedema Surgery
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 血管柄付きリンパ節移植における移植リンパ節の血流2021

    • Author(s)
      秋田新介
    • Organizer
      第30回日本形成外科学会基礎学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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