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The role of progranulin in the pathogenesis of inflammatory skin diseases

Research Project

Project/Area Number 19K08788
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionAsahi University (2022-2023)
Gifu University (2019-2021)

Principal Investigator

SeishimaThe Mariko  朝日大学, 歯学部, 教授 (00171314)

Co-Investigator(Kenkyū-buntansha) 水谷 陽子  岐阜大学, 医学部附属病院, 講師 (60759950)
Project Period (FY) 2019-04-01 – 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 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsプログラニュリン / 乾癬 / アトピー性皮膚炎 / サイトカイン / progranulin / 炎症性皮膚疾患
Outline of Research at the Start

プログラニュリン(PGRN)は表皮細胞で発現し、特に乾癬表皮で発現が増加しているが、その意義は不明である。本研究では重要な炎症性皮膚疾患である乾癬およびアトピー性皮膚炎について、患者血清中のPGRN濃度測定、皮疹組織におけるPGRNの発現、培養表皮細胞を用いてPGRNのサイトカイン産生に対する作用を検討する。また、これらの疾患のモデルマウスを作成し、血清中、皮疹の組織中のPGRN濃度を測定する。本研究は乾癬とアトピー性皮膚炎の病態におけるPGRNの役割を明らかにするとともにPGRN及びそのアナログであるAtsttrinを用いた新規治療の開発に寄与すると考えられる。

Outline of Final Research Achievements

Serum PGRN (progranulin) concentrations were significantly increased in psoriasis compared to healthy subjects and were positively correlated with PASI (psoriasis area and severity index) score, a clinical marker of psoriasis. We also found a correlation with serum PGRN concentrations and serum IL-17 and IL-22 concentrations. PGRN concentrations were significantly higher in sera from patients with atopic dermatitis and correlated positively with TARC (thymus and activation-regulated chemokine) and IL-36γ concentrations.
The effects of PGRN on cultured epidermal cells were examined: IL-23 expression in epidermal cells was increased when PGRN was added to the culture medium. Furthermore, the expression of PGRN was significantly increased by the addition of IL-22, IL-36γ, and TNF-α to the culture medium. These results suggest that PGRN plays a role in the pathogenesis of psoriasis and atopic dermatitis via cytokines.

Academic Significance and Societal Importance of the Research Achievements

プログラニュリンはサイトカイン産生を介して乾癬、アトピー性皮膚炎などの皮膚疾患の病態形成に関与することが明らかになり、今後の病態解明と創薬に役立つと考えられる。

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

    (8 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Serum Profiles of Tryptophan-Kynurenine Pathway Metabolites in Psoriasis.2021

    • Author(s)
      Mariko Seishima, Yasuko Yamamoto, Masashi Sakurai, Rika Sakai, Kento Fujii, Yoko Mizutani, Kuniaki Saito.
    • Journal Title

      Explor Immunol.

      Volume: 1 Pages: 258-268

    • DOI

      10.37349/ei.2021.00017

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indoleamine 2,3-Dioxygenase 2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation2020

    • Author(s)
      Fujii K, Yamamoto Y, Mizutani Y, Saito K, Seishima M
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 15 Pages: 5515-5515

    • DOI

      10.3390/ijms21155515

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of STING signaling accelerates skin wound healing.2020

    • Author(s)
      Mizutani Y, Kanbe A, Ito H, Seishima M.
    • Journal Title

      J Dermatol Sci.

      Volume: 97 Issue: 1 Pages: 21-29

    • DOI

      10.1016/j.jdermsci.2019.11.008

    • Related Report
      2019 Research-status Report
  • [Journal Article] IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model.2019

    • Author(s)
      Kanoh H, Ishitsuka A, Fujine E, Matsuhaba S, Nakamura M, Ito H, Inagaki N, Banno Y, Seishima M.
    • Journal Title

      J Immunol Res.

      Volume: 2019 Pages: 1-10

    • DOI

      10.1155/2019/3030268

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generalized Pustular Psoriasis With CARD14 Variant c.526G>C (p.Asp176His) Successfully Treated With Granulocyte and Monocyte Adsorption Apheresis.2019

    • Author(s)
      Fujii A, Fujii K, Seishima M.
    • Journal Title

      Ther Apher Dial.

      Volume: 23 Issue: 3 Pages: 298-299

    • DOI

      10.1111/1744-9987.12816

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Management of psoriatic patients in biologics era2019

    • Author(s)
      Seishima M
    • Organizer
      Beijing Psoriasis Symposium
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Treatment for psoriasis during pregnancy2019

    • Author(s)
      Seishima M
    • Organizer
      The 4th Xi’an International Psoriasis Forum
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Activation of STING signaling accelerates skin wound healing2019

    • Author(s)
      Hattori Y, Kanbe A, Ito H, Seishima M
    • Organizer
      49th Annual European Society for Dermatoligicail Research Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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