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Study on collagen dipeptides on growth of mesenchymal stem cells

Research Project

Project/Area Number 19H02911
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionKyoto University

Principal Investigator

Sato Kenji  京都大学, 農学研究科, 教授 (00202094)

Co-Investigator(Kenkyū-buntansha) 重村 泰毅  東京家政大学短期大学部, 短期大学部, 准教授 (20373178)
自見 至郎  福岡大学, 公私立大学の部局等, 研究特任教授 (30226360)
淺井 智子  奈良女子大学, 生活環境科学系, 助教 (50832036)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Keywordsコラーゲン / 線維芽細胞 / Pro-Hyp / 創傷治癒 / 瘢痕化 / コラーゲンペプチド / 間葉系幹細胞 / p75NTR
Outline of Research at the Start

間葉系幹細胞マーカーである低親和性神経成長因子受容体(p75NTR)に着目して、Pro-Hyp等のコラーゲンジペプチドが特定の状態にある線維芽細胞に対してのみ増殖促進効果を持つことを明らかにする。マウス皮膚から遊走してきた線維芽細胞、および個体組織中の線維芽細胞の間葉系成体幹細胞マーカーの有無、およびコラーゲンペプチドの取り込み能を検討する。さらに、Pro-Hypの細胞増殖促進効果がこれらの性質により変化することを確認する。本研究によりコラーゲンペプチドの摂取によりなぜ正常組織の繊維化が生じずに創傷治癒が促進されるかを説明できることが期待できる。

Outline of Final Research Achievements

Pro-Hyp increases in human blood after oral administration of collagen peptide. The present study revealed that primary cultured fibroblasts migrated from mouse skin expressed mesenchymal stem cell marker (p75NTR) at first day but its expression decreased after growth. Fluorophore (FITC)-labeled Pro-Hyp was specifically incorporated into p75NTR-positive fibroblasts but not into the p75NTR negative ones. Pro-Hyp enhanced growth of the p75NTR-positive fibroblasts but not the p75NTR-negative ones. These facts indicate that food-derived Pro-Hyp can enhance growth of the p75NTR positive fibroblasts accumulating to wound healing sites but exert little effect on resident fibroblasts in normal tissues. In animal models, Pro-Hyp can enhance wound healing and suppress scarring.

Academic Significance and Societal Importance of the Research Achievements

コラーゲンペプチドの摂取により血中で増加するPro-Hypは正常組織の成熟した線維芽細胞には影響することなく、創傷治癒部位に集積する分化直後の線維芽細胞の増殖を促進することが明らかにした。この結果は、コラーゲンペプチドの摂取は正常組織に過剰な線維化を起こすことなく、創傷治癒を促進することを説明できる。さらに動物モデルにおいてもコラーゲンペプチド由来のPro-Hypは真皮の創傷治癒を促進することを確認した。さらに筋膜切除後の治癒においての瘢痕化も抑制した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 6 results) Book (2 results)

  • [Journal Article] Metabolic Fate and Bioavailability of Food-Derived Peptides: Are Normal Peptides Passed through the Intestinal Layer To Exert Biological Effects via Proposed Mechanisms?2022

    • Author(s)
      Sato Kenji
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: 70 Issue: 5 Pages: 1461-1466

    • DOI

      10.1021/acs.jafc.1c07438

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Collagen-derived dipeptide Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall in mice2021

    • Author(s)
      Jimi Shiro、Koizumi Seiko、Sato Kenji、Miyazaki Motoyasu、Saparov Arman
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-021-98407-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing2020

    • Author(s)
      Sato Kenji、Asai Tomoko T.、Jimi Shiro
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 548975-548975

    • DOI

      10.3389/fcell.2020.548975

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mouse skin fibroblasts with mesenchymal stem cell marker p75 neurotrophin receptor proliferate in response to prolyl-hydroxyproline2020

    • Author(s)
      Asai Tomoko T.、Yoshikawa Kazunobu、Sawada Kazuhiro、Fukamizu Kazuna、Koyama Yoh-ichi、Shigemura Yasutaka、Jimi Shiro、Sato Kenji
    • Journal Title

      Journal of Functional Foods

      Volume: 66 Pages: 103792-103792

    • DOI

      10.1016/j.jff.2020.103792

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Food-Derived Collagen Peptides, Prolyl-Hydroxyproline (Pro-Hyp), and Hydroxyprolyl-Glycine (Hyp-Gly) Enhance Growth of Primary Cultured Mouse Skin Fibroblast Using Fetal Bovine Serum Free from Hydroxyprolyl Peptide2019

    • Author(s)
      Asai Tomoko T.、Oikawa Fumi、Yoshikawa Kazunobu、Inoue Naoki、Sato Kenji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 1 Pages: 229-229

    • DOI

      10.3390/ijms21010229

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Pro-Hyp 添 加 に よ る 培 養 マ ウ ス 皮 膚 中 p75NTR 陽性細胞の変化2022

    • Author(s)
      淺井 智子、関野 朱夏、高村 仁知、 佐藤 健司
    • Organizer
      第76回日本栄養・食糧学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] コラーゲンペプチドの線維芽細胞への働き2021

    • Author(s)
      佐藤健司
    • Organizer
      第39回日本美容皮膚科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 肌のサプリメント2021

    • Author(s)
      佐藤健司
    • Organizer
      第15回見た目のアンチエイジング研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] コラーゲン・エラスチンペプチド摂取による効果とその活性成分2020

    • Author(s)
      佐藤健司
    • Organizer
      第84回日本皮膚科学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] コラーゲンペプチドの効果のメカニズム2020

    • Author(s)
      佐藤健司
    • Organizer
      日本香粧学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Food-derived and endogenous collagen peptide, Pro-Hyp -Function and target cell-2019

    • Author(s)
      Sato, K.
    • Organizer
      International Conference of Food Factors
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pro-Hyp, food-derived collagen peptide in blood, enhances growth of fibroblasts expressing p75NTR, somatic stem cell marker2019

    • Author(s)
      Asai, T.
    • Organizer
      2nd International Symposium on Bioactive Peptides
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Biologically Active Peptides From Basic Science to Applications for Human Health2021

    • Author(s)
      Kenji Sato
    • Publisher
      ELSEVIA
    • ISBN
      9780128214381
    • Related Report
      2021 Annual Research Report
  • [Book] コラーゲン 基礎から応用 第11章 消化と吸収2020

    • Author(s)
      佐藤健司・重村泰毅
    • Total Pages
      7
    • Publisher
      株式会社インプレス
    • ISBN
      9784844379140
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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