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Development of new treatment for psoriasis targeting CD147/basigin

Research Project

Project/Area Number 21K08329
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKagoshima University

Principal Investigator

kanekura takuro  鹿児島大学, 医歯学域医学系, 教授 (70177509)

Co-Investigator(Kenkyū-buntansha) 古川 龍彦  鹿児島大学, 医歯学域医学系, 教授 (40219100)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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)
KeywordsCD147/Basigin / 乾癬 / T細胞分化 / Th17細胞 / モノカルボン酸トランスポータ / モノカルボン酸トランスポーター / AP-9 / 解糖系 / MCT
Outline of Research at the Start

CD147/basiginは免疫グロブリンスーパーファミリーに属する多機能性の分子で、エネルギー代謝系である解糖系を制御している。T細胞は分化・活性化のエネルギーを解糖系に依存する。我々はCD147/basiginが解糖系の調節を介して、CD4+T細胞のTh17細胞への分化を促し乾癬の病態形成に関与していることを明らかにした。この知見をもとに、申請者らはCD147/basiginを標的とする乾癬の新規治療を開発することを目的に本研究を計画した。

Outline of Final Research Achievements

We demonstrated that CD147/basigin regulates cancer cell proliferation and invasion through the glycolytic pathway. Recent studies showed that differentiation and activation of T lymphocytes also depend on glycolysis for energy. We revealed that CD147 is involved in the development of psoriasis, an immunological disease caused by abnormal differentiation and proliferation of T cells. CD147 promotes the differentiation of naive T cells into Th17 cells which play the pivotal role in psoriasis. The development of experimental psoriasis was suppressed in the mice deficient in CD147 gene. Based on these findings, we planned this research with the aim of developing a new treatment for psoriasis that inhibits glycolysis targeting CD147. In silico virtual screening resulted in a list of 183 candidate compounds. Among these compounds, we identified several compounds that inhibit the differentiation of CD4+ T cells into Th17 cells through suppression of glycolysis and are not cytotoxic.

Academic Significance and Societal Importance of the Research Achievements

乾癬はCD4+ T細胞が種々の因子の刺激によりTh17細胞へ分化しIL-17の産生が亢進することにより発症する。近年使用される生物学的製剤はサイトカインを標的とし、JAK阻害薬やPDE4阻害薬はサイトカイン産生を抑制する。CD147/basiginを標的とする治療はCD4+ T細胞のサイトカイン産生細胞への分化を抑制することを目的としており、従来の治療とは全く異なるより根本的な治療である。乾癬の治療は日進月歩の観を呈している。しかし本症は難治性皮膚疾患であり未だに完治しない症例が少なくない。この研究成果は新たな治療法の開発に結び付く可能性が高く社会的意義を有する。

Report

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

    (11 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 11 results)

  • [Journal Article] Hair follicle damage by 100-mGy low-dose fractionated X-irradiation and protective effects of TEMPOL, a stable nitroxide radical, against irradiation.2024

    • Author(s)
      Kawabata Y, Fukushige T, Indo HP, Matsumoto K, Ueno M, Nakanishi I, Chatatikun M, Klangbud WK, Surinkaew S, Tangpong J, Kanekura T, Majima H.
    • Journal Title

      Radiat Res

      Volume: 201 Issue: 2 Pages: 115-115

    • DOI

      10.1667/rade-23-00167.1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Orexin neurons play contrasting roles in itch and pain neural processing via projecting to the periaqueductal gray2024

    • Author(s)
      Kaneko Tatsuroh、Oura Asuka、Imai Yoshiki、Kusumoto-Yoshida Ikue、Kanekura Takuro、Okuno Hiroyuki、Kuwaki Tomoyuki、Kashiwadani Hideki
    • Journal Title

      Communications Biology

      Volume: 7 Issue: 1 Pages: 290-290

    • DOI

      10.1038/s42003-024-05997-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpressed perforin contributes to the melanocyte destruction via epigenetic regulation in patients with vitiligo2023

    • Author(s)
      Deng Q,Zou P,Du P, Shi Y, Pi Z, Xiao Y, Kanekura T, Zhand H,ZhanY, Qiu X, Ding Y, Zheng Z, Xiao Z
    • Journal Title

      Int Immunopharmacol

      Volume: 114 Pages: 109574-109574

    • DOI

      10.1016/j.intimp.2022.109574

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neutrophil-Derived MicroRNA-1290 Promotes Keratinocyte Proliferation in Psoriasis2023

    • Author(s)
      Higashi Yuko、Yamakuchi Munekazu、Ibusuki Atsuko、Okubo Aoi、Fukushige Tomoko、Hashiguchi Teruto、Kanekura Takuro
    • Journal Title

      Journal of Investigative Dermatology

      Volume: - Issue: 7 Pages: 03209-8

    • DOI

      10.1016/j.jid.2023.10.042

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD147/Basigin is involved in the development of malignant tumors and T cell-mediated immunological disorders via regulation of glycolysis.2023

    • Author(s)
      Kanekura T
    • Journal Title

      Int J Mol Sci

      Volume: 24 Issue: 24 Pages: 17344-17344

    • DOI

      10.3390/ijms242417344

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Granulocyte and monocyte adsorptive apheresis for pyoderma gangrenosum2022

    • Author(s)
      Higashi Y*, Ibusuki A, Baba N, Hatanaka M, Tada KI, Kanekura T.
    • Journal Title

      Ther Apher Dial

      Volume: 26 Issue: 2 Pages: 450-455

    • DOI

      10.1111/1744-9987.13720

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of distinct N-glycosylation patterns on extracellular vesicles from small-cell and non-small-cell lung cancers cells.2022

    • Author(s)
      Kondo Kiyotaka, Harada Yoichiro, Nakano Miyako, Suzuki Takehiro, Fukushige Tomoko, Hanzawa Ken, Yagi Hirokazu, Takagi Koichi, Mizuno Keiko, Miyamoto Yasuhide, Taniguchi Naoyuki, Kato Koichi, Kanekura Takuro, Dohmae Naoshi, Machida Kentaro, Maruyama Ikuro, Inoue Hiromasa
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298(6) Issue: 6 Pages: 101950-101950

    • DOI

      10.1016/j.jbc.2022.101950

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice2022

    • Author(s)
      4.Yamasuji-Maeda Y, Nishimori H, Seike K, Yamamoto A, Fujiwara H, Kuroi T, Saeki K, Fujinaga H, Okamoto S, Matsuoka K, Fujii N, Tanaka T, Fujii M, Mominoki K, Kanekura T, Maeda Y.
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 9 Pages: 0273749-0273749

    • DOI

      10.1371/journal.pone.0273749

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resident human dermal γδT-cells operate as stress-sentinels: Lessons from the hair follicle2021

    • Author(s)
      Uchida Y, Gherardini J, Pappelbaum K, Cheret J, Schulte-Mecklenbeck A, Gross C, Strbo N, Gilhar A, Kanekura T,
    • Journal Title

      J Autoimmun

      Volume: 124 Pages: 102711-102711

    • DOI

      10.1016/j.jaut.2021.102711

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD147 is Essential for the Development of Psoriasis via the induction of Th17 Cell Differentiation.2021

    • Author(s)
      Aoi Okubo, Youhei Uchida, Yuko Higashi, Takuya Sato, Youichi Ogawa, Akihiro Ryuge, Kenji Kadomatsu, Takuro Kanekura.
    • Journal Title

      International Journal of Molecular Sciences.

      Volume: 23(1) Issue: 1 Pages: 177-177

    • DOI

      10.3390/ijms23010177

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Depletion of HSP72 by siRNA and Quercetin Enhances Vorinostat-Induced Apoptosis in an HSP72-Overexpressing Cutaneous T-Cell Lymphoma Cell Line, Hut78.2021

    • Author(s)
      Fujii K, Idogawa M, Suzuki N, Iwatsuki K, Kanekura T.
    • Journal Title

      Int J Mol Sci.

      Volume: 22 Issue: 20 Pages: 11258-11258

    • DOI

      10.3390/ijms222011258

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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