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Elucidation of the mechanism of early vascular permeability enhancement that induces ulcerative colitis

Research Project

Project/Area Number 19K17414
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Saijo Hiroki  東京慈恵会医科大学, 医学部, 講師 (10794654)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords潰瘍性大腸炎 / dextran sulfate sodium / 炎症性腸疾患 / DSS / miR-155 / Tenascin C / DSS誘発腸炎マウス
Outline of Research at the Start

再燃と寛解を繰り返す炎症性腸疾患(IBD)は、長期間の寛解維持がQOLの向上に直結するが、現行の治療法で再燃防止を長期維持できている症例は少ない。申請者は、潰瘍性大腸炎のモデルマウスにおいて、粘膜内の血管障害が粘膜上皮障害を誘発し,その後の腸炎悪化に神経細胞の過剰興奮が関与していることを報告した。このことは血管、上皮、神経の恒常性の保持により長期間の寛解が維持できることを示唆している。このような背景から本研究では、特に血管構造の安定化に関与する特異的な遺伝子を探索することで、大腸粘膜の恒常性維持機構および炎症制御メカニズムを解明し、将来的にIBDにおける寛解維持療法への応用を目指す。

Outline of Final Research Achievements

Dextran sulfate sodium (DSS) colitis mice are frequently used as a disease model for ulcerative colitis, but the pathogenesis of this colitis is unknown. Microcirculatory disturbances in the colonic mucosa are considered to be involved in the development of DSS colitis. However, early structural changes in the local vasculature have not been adequately investigated. Therefore, we identified the cause of early hemorrhage in DSS colitis and closely examined the relationship between blood circulation and the mucosal environment in the mouse colon. As a result, it was found that vascular injury occurred in the mid-colon, the perfusion area of the superior mesenteric artery and inferior mesenteric artery, preceding mucosal damage, and then extended to the distal colon. Furthermore, it was revealed that the hemorrhage originated from the arterial plexus in the deep mucosa.

Academic Significance and Societal Importance of the Research Achievements

DSS大腸炎において、粘膜障害の前段階として、粘膜固有層深部の動脈叢で早期の血管障害が観察された。この発見は、ヒトの潰瘍性大腸炎においても同様の現象が見られる可能性が考えられる。そのため内視鏡検査による粘膜血管系の観察を通じて、病変を早期に発見し、適切な治療介入を行うことができると期待される。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] The role of Tenascin C during the development of DSS induced colitis2021

    • Author(s)
      Saijo H*, Hoshino A*, Tatsumi N, Arihiro S, Okabe M, Saruta M, Kusakabe M, Hashimoto H (*equally contributed))
    • Journal Title

      Jikeikai Medical Journal

      Volume: 68 Pages: 67-79

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of TNC during the development of DSS induced colitis2021

    • Author(s)
      Atushi Hoshino, Hiroki Saijo(equally contributed), Norifumi Tatsumi, Seiji Arihiro, Masataka Okabe, Masayuki Saruta, Moriaki Kusakabe, Hisashi Hashimoto
    • Journal Title

      Jikeikai Medical Journal

      Volume: in press

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

URL: 

Published: 2019-04-18   Modified: 2025-01-30  

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