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Impact of skin bacteria and cellular senescence on cutaneous tumor malignant conversion

Research Project

Project/Area Number 20K07446
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionOsaka University

Principal Investigator

Kawamoto Shimpei  大阪大学, 微生物病研究所, 助教 (40612081)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords皮膚細菌 / 細胞老化 / 線維芽細胞 / 皮膚腫瘍
Outline of Research at the Start

皮膚培養細胞を皮膚細菌の上清や菌体と培養することで皮膚細菌による細胞老化誘導機構を明らかにするとともに、菌体もしくは菌体培養上清に含まれる細胞老化誘導因子を同定する。次に、皮膚腫瘍モデルマウスを用いて皮膚腫瘍の病態における細胞老化および皮膚細菌の関与を検討し、さらに皮膚細菌由来の細胞老化誘導因子の病態への影響を明らかにする。最後に、この因子をもたない皮膚細菌欠損株を皮膚腫瘍モデルマウスに塗布することで、この因子が皮膚における細胞老化誘導や皮膚腫瘍の悪性化に関与しているのかを確認する。
以上により、皮膚細菌による細胞老化を介した皮膚腫瘍悪性化機構を明らかにする。

Outline of Final Research Achievements

By establishing a new detection method for senescent cells, we found that cellular senescence is induced in dermal fibroblasts at the site of skin tumors. Furthermore, we found that cellular senescence is induced in dermal fibroblasts via metabolites secreted by skin bacteria. The induction of cellular senescence in dermal fibroblast leads to abnormal proliferation of epidermal cells and accelerates the malignant transformation of skin tumors. These findings provide a partial picture of the mechanism of skin cancer promotion via the induction of cellular senescence by skin bacteria.

Academic Significance and Societal Importance of the Research Achievements

老化や様々な疾患発症の原因となることが知られるものの、検出が困難であった老化細胞の新規検出法の確立により、老化細胞を対象とした研究のさらなる発展に貢献できる。さらに、生体内の細胞老化誘導に関わる因子として皮膚細菌の重要性が明らかとなった。細胞の誘導因子また、皮膚腫瘍の悪性化に関与することが明らかとなった皮膚細菌や老化細胞を標的とすることで、皮膚腫瘍の新規治療法の開発につながる。

Report

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

    (7 results)

All 2022 2021 2020

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

  • [Journal Article] The 6th international cell senescence association conference2022

    • Author(s)
      Kawamoto Shimpei、Matsumoto Tomonori、Takasugi Masaki、Hara Eiji
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 8 Pages: 517-525

    • DOI

      10.1111/gtc.12970

    • Related Report
      2022 Annual Research Report
  • [Journal Article] SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response2022

    • Author(s)
      Tsuji Shunya、Minami Shohei、Hashimoto Rina、Konishi Yusuke、Suzuki Tatsuya、Kondo Tamae、Sasai Miwa、Torii Shiho、Ono Chikako、Shichinohe Shintaro、Sato Shintaro、et al.
    • Journal Title

      Nature Aging

      Volume: 2 Issue: 2 Pages: 115-124

    • DOI

      10.1038/s43587-022-00170-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion2021

    • Author(s)
      Okumura Shintaro、Konishi Yusuke、Narukawa Megumi、Sugiura Yuki、Yoshimoto Shin、Arai Yuriko、Sato Shintaro、Yoshida Yasuo、Tsuji Shunya、Uemura Ken、Wakita Masahiro、Matsudaira Tatsuyuki、Matsumoto Tomonori、Kawamoto Shimpei、Takahashi Akiko、Itatani Yoshiro、Miki Hiroaki ら
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 5674-5674

    • DOI

      10.1038/s41467-021-25965-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expansion of senescent megakaryocyte-lineage cells maintains CML cell leukemogenesis2020

    • Author(s)
      Tanabe Yamato、Kawamoto Shimpei、Takaku Tomoiku、Morishita Soji、Hirao Atsushi、Komatsu Norio、Hara Eiji、Mukaida Naofumi、Baba Tomohisa
    • Journal Title

      Blood Advances

      Volume: 4 Issue: 24 Pages: 6175-6188

    • DOI

      10.1182/bloodadvances.2020003117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells.2020

    • Author(s)
      Wakita M, Takahashi A, Sano O, Loo TM, Imai Y, Narukawa M, Iwata H, Matsudaira T, Kawamoto S, Ohtani N, Yoshimori T, Hara E.
    • Journal Title

      Nat Commun

      Volume: 1935 Issue: 1 Pages: 1935-1935

    • DOI

      10.1038/s41467-020-15719-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification and characterization of skin bacteria involved in obesity-induced skin carcinogenesis in mice2021

    • Author(s)
      Ken Uemura, Olivia MIsaki Kyama, Shimpei Kawamoto, Masahiro Wakita, Eiji Hara
    • Organizer
      6th International Cell Senescence Association(ICSA)Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification and characterization of skin bacteria involved in skin carcinogenesis in mice2020

    • Author(s)
      Ken Uemura, Shimpei Kawamoto, Masahiro Wakita, Eiji Hara
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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