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Novel intestinal anti-inflammatory therapies by regulating adhesion molecule transport by the CUL3 ubiquitin ligase.

Research Project

Project/Area Number 18K15822
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionNagoya City University

Principal Investigator

ozeki Keiji  名古屋市立大学, 医薬学総合研究院(医学), 講師 (70750610)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords炎症性腸疾患 / 接着分子 / インテグリン / 細胞接着因子 / cullin3 / 難治性炎症性腸疾患 / Cullin3 / CUL3ユビキチンE3リガーゼタンパク質 / 血管内皮細胞 / BTB-ZnF ドメイン蛋白 / CUL3ユビキチンリガーゼ
Outline of Final Research Achievements

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. We investigated whether regulating the Cullin-3 (CUL3) ubiquitin (Ub)E3 ligase protein complex, a membrane transport regulator of cell adhesion factors, could be a new therapeutic strategy for UC treatment by targeting intracellular membrane transport of cell adhesion factors in vascular endothelial cells and leukaemic cells. E-selection, ICAM-1, ICAM-2, VCAM-1, MAdCAM-1 and integrin α- and β-chains under CUL3 gene knockdown in human umbilical vein endothelial cells (HUVEC) and human leukaemia cell lines, respectively, by Western blot (WB) method. Subcellular localisation analysis of integrin α- and β-chains by fluorescence immunostaining and protein level variation analysis using the Western blot (WB) method confirmed that the expression levels of integrin α- and β-chains were reduced, and then AlphaScreening was used to identify the responsible BTBP, but the appropriate target protein could not be identified.

Academic Significance and Societal Importance of the Research Achievements

現在本邦をはじめ潰瘍性大腸炎の患者は右肩上がりの増加を認めている。多くの新規のサイトカインや接着分子などリンパ球のトラフィッキングに関わる薬剤の新規開発が近年認められる。しかし、残念ながら今のところすべてを解決する治療法は確立されていない。今後も、既存治療効果を高め、更なる新規機序の薬剤開発の継続は必要だと考えられて今回の研究成果は今後の潰瘍性大腸炎の治療効果を高めていく可能性がある。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 9 results)

  • [Journal Article] Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor2023

    • Author(s)
      Tanida S, Ozeki K, Katano T, Tanaka M, Shimura T, Kubota E, Kataoka H, Takahama T, Sasoh S, Kubota Y, Ban T, Ando T, Nakamura M, Joh T.
    • Journal Title

      J Clin Med Res.

      Volume: 3 Issue: 3 Pages: 181-186

    • DOI

      10.14740/jocmr4887

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase II Prospective Study of Trastuzumab in Combination with S-1 and Oxaliplatin (SOX100) Therapy for HER2-Positive Advanced Gastric Cancer2022

    • Author(s)
      Mori Y, Kataoka H, Ebi M, Adachi K, Yamaguchi Y, Hayashi N, Hirata Y, Sobue S, Ishihara R, Suzuki Y, Mizushima T, Inoue Y, Hasegawa I, Ono S, Hirano A, Kimura Y, Seno K, Ozeki K, Shimura T, Kubota E.
    • Journal Title

      J Gastrointest Cancer

      Volume: 4 Issue: 4 Pages: 930-938

    • DOI

      10.1007/s12029-021-00711-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aseptic Abscess Syndrome With Ulcerative Colitis and Pyoderma Gangrenosum2022

    • Author(s)
      Ozeki K, Tanida S, Kataoka H.
    • Journal Title

      Clin Gastroenterol Hepatol.

      Volume: 10 Issue: 10 Pages: 27-27

    • DOI

      10.1016/j.cgh.2022.04.040

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models.2021

    • Author(s)
      Sasaki M, Tanaka M, Ichikawa H, Suzuki T, Nishie H, Ozeki K, Shimura T, Kubota E, Tanida S, Kataoka H
    • Journal Title

      PLoS One

      Volume: 16 Issue: 4 Pages: e0249650-e0249650

    • DOI

      10.1371/journal.pone.0249650

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis2021

    • Author(s)
      Tanida S, Ozeki K, Kanno T, Katano T, Sugimura N, Nishie H, Iwasaki H, Tanaka M, Shimura T, Kubota E, Kataoka H.
    • Journal Title

      J Clin Med Res

      Volume: Nov;13(10-11) Issue: 10-11 Pages: 510-514

    • DOI

      10.14740/jocmr4625

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma2020

    • Author(s)
      Okuda Y, Shimura T, Iwasaki H, Katano T, Kitagawa M, Nishigaki R, Fukusada S, Natsume M, Tanaka M, Nishie H, Ozeki K, Yamada T, Kataoka H.
    • Journal Title

      Digestion.

      Volume: Oct 13 Issue: 4 Pages: 1-10

    • DOI

      10.1159/000510993

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis2020

    • Author(s)
      Tanida S, Ozeki K, Mizoshita T, Kitagawa M, Ozeki T, Tanaka M, Nishie H, Shimura T, Kubota E, Kataoka H.
    • Journal Title

      J Clin Med Res. 2020

      Volume: 1 Issue: 1 Pages: 36-40

    • DOI

      10.14740/jocmr4037

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis.2020

    • Author(s)
      Tanida S, Ozeki K, Mizoshita T, Kitagawa M, Ozeki T, Tanaka M, Nishie H, Shimura T, Kubota E, Kataoka H.
    • Journal Title

      J Clin Med Res.

      Volume: 12(1) Pages: 36-40

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer.2019

    • Author(s)
      Shimura T, Iwasaki H, Kitagawa M, Ebi M, Yamada T, Yamada T, Katano T, Nisie H, Okamoto Y, Ozeki K, Mizoshita T, Kataoka H.
    • Journal Title

      Transl Oncol.

      Volume: 12(3) Issue: 3 Pages: 539-544

    • DOI

      10.1016/j.tranon.2018.12.006

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease.2018

    • Author(s)
      Tanida S, Mizoshita T, Ozeki K, Katano T, Tanaka M, Nishie H, Shimura T, Okamoto Y, Kubota E, Kataoka H, Joh T.
    • Journal Title

      Ther Apher Dial.

      Volume: 22 Issue: 3 Pages: 295-300

    • DOI

      10.1111/1744-9987.12697

    • Related Report
      2018 Research-status Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2024-01-30  

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