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Intracellular labile heme: signaling function in cell differentiation and proliferation

Research Project

Project/Area Number 18K19423
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionUniversity of Fukui

Principal Investigator

Sugai Manabu  福井大学, 学術研究院医学系部門, 教授 (90303891)

Co-Investigator(Kenkyū-buntansha) 南部 由希子  福井大学, 学術研究院医学系部門, 准教授 (70580380)
林 達成  福井大学, 学術研究院医学系部門, 特命助教 (80781111)
Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsヘム / 細胞分化 / 細胞増殖 / 分化 / 増殖 / ミトコンドリア
Outline of Final Research Achievements

The signaling function of free-heme in cell differentiation processes is a new concept that has only recently emerged and the supporting physiological evidences for it were provided by the two research groups, including us. However, its relevance cannot be evaluated precisely because a reliable free-heme sensor is not yet available. In this project, we developed free-heme sensor to verify and examine the physiological role of free-heme as a signaling molecule within various types of cells.

Academic Significance and Societal Importance of the Research Achievements

ヘムに結合する転写因子(分化、老化、リズムに関わる)が多数見出されたため、細胞分化や細胞機能制御因子としてのヘムの役割に注目が集まっている。最近生理的条件下でヘムが分化制御因子として機能していることを申請者を含む二つのグループが明らかにした。このヘムによる分化制御機能の一般性をさらに詳細に解析するためには、実際に生体内で制御因子として機能している「細胞内遊離ヘム」を感度良く特異的に検出するプローブを開発することが必要である。本研究課題において開発に成功したことから、ようやく「細胞内遊離ヘム」の生理的機能を明らかにすることが可能になったと考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results)

  • [Journal Article] Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling2021

    • Author(s)
      Murashima-Suginami A.、Kiso H.、Tokita Y.、Mihara E.、Nambu Y.、Uozumi R.、Tabata Y.、Bessho K.、Takagi J.、Sugai M.、Takahashi K.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 7

    • DOI

      10.1126/sciadv.abf1798

    • NAID

      120006958083

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homeostatic Function of Dermokine in the Skin Barrier and Inflammation.2020

    • Author(s)
      Akira Utsunomiya, Takenao Chino, Natsuko Utsunomiya, Vu Huy Luong, Atsushi Tokuriki, Tatsuro Naganuma, Makoto Arita, Kiyoshi Higashi, Koichi Saito, Noriyuki Suzuki, Ayako Ohara, Manabu Sugai, Koji Sugawara, Daisuke Tsuruta, Noritaka Oyama, Minoru Hasegawa
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 140 Issue: 4 Pages: 838-849

    • DOI

      10.1016/j.jid.2019.09.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of tooth regenerative medicine strategies by controlling the number of teeth using targeted molecular therapy2020

    • Author(s)
      Takahashi Katsu、Kiso Honoka、Murashima-Suginami Akiko、Tokita Yoshihito、Sugai Manabu、Tabata Yasuhiko、Bessho Kazuhisa
    • Journal Title

      Inflammation and Regeneration

      Volume: 40 Issue: 1 Pages: 21-21

    • DOI

      10.1186/s41232-020-00130-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dephosphorylation of protamine 2 at serine 56 is crucial for murine sperm maturation in vivo2019

    • Author(s)
      Itoh Katsuhiko、Kondoh Gen、Miyachi Hitoshi、Sugai Manabu、Kaneko Yoshiyuki、Kitano Satsuki、Watanabe Hitomi、Maeda Ryota、Imura Akihiro、Liu Yu、Ito Chizuru、Itohara Shigeyoshi、Toshimori Kiyotaka、Fujita Jun
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 574 Pages: 7232-7234

    • DOI

      10.1126/scisignal.aao7232

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S2019

    • Author(s)
      Nitta A, Hori K, Tanida I, Igarashi A, Deyama Y, Ueno T, Kominami E, Sugai M, Aoki K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 508(2) Issue: 2 Pages: 521-526

    • DOI

      10.1016/j.bbrc.2018.11.158

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immune responses against Lewis Y tumor-associated carbohydrate antigen displayed densely on self-assembling nanocarriers2018

    • Author(s)
      Yamazaki Yuji、Nambu Yukiko、Ohmae Masashi、Sugai Manabu、Kimura Shunsaku
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 16 Issue: 43 Pages: 8095-8105

    • DOI

      10.1039/c8ob01955j

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct evidence for the age-dependent demise of GNAS -mutated cells in oral fibrous dysplasia2018

    • Author(s)
      Isobe Yu、Takahashi Katsu、Kiso Honoka、Nakao Kazumasa、Ikeno Masayuki、Koyama Noriaki、Sugai Manabu、Shimizu Akira、Haga Hironori、Bessho Kazuhisa
    • Journal Title

      Archives of Oral Biology

      Volume: 93 Pages: 133-140

    • DOI

      10.1016/j.archoralbio.2018.05.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research

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Published: 2018-07-25   Modified: 2022-01-27  

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