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Challenge to control the palatal scar formation and to analyze the regulatory mechanizm of metabolic reprogramming via hypoxia inducible genes

Research Project

Project/Area Number 17K19758
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Oral Science and related fields
Research InstitutionThe University of Tokushima

Principal Investigator

IZAWA Takashi  徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (30380017)

Co-Investigator(Kenkyū-buntansha) 田中 栄二  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (40273693)
泰江 章博  徳島大学, 病院, 講師 (80380046)
岩浅 亮彦  徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (90746025)
森 浩喜  徳島大学, 病院, 医員 (90779985)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords低酸素応答遺伝子 / 口蓋瘢痕 / 創傷治癒 / 代謝リプログラミング / 歯学
Outline of Final Research Achievements

The blood flow in the wound scar region is known to be decreased compared to the surrounding area of the wound closure. Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that HIF-1α signaling is involved in wound healing by regulating inflammatory cytokines such as such as TNF-α, MIP-1α, and MCP-1. Here, we investigated the role of HIF-1α signaling on M1/M2-like macrophage expression of heterozygous HIF-1α-deficient (HIF-1α HET) mice palatal wound healing. Histological examination showed that palatal wound closure in HIF-1α HET mice was delayed by the decreased infiltration of M1/M2 macrophage markers in parallel with the diminished production of Col1a1, MCP-1, MIP-1α compared with WT mice. These results suggest that HIF-1α signaling may play an important role in the regulation of palatal wound healing and HIF-1α deficiency aggravate the infiltration of M1/M2 macrophage.

Academic Significance and Societal Importance of the Research Achievements

口唇口蓋裂患者における裂隙閉鎖術後の瘢痕組織はその強い瘢痕鈎縮により、上顎裂成長や上顎歯列弓狭窄をもたらし、患者は重篤な不正咬合を呈する。また矯正歯科治療施術後も歯の後戻りの原因となり、歯列・咬合の安定を非常に困難にさせることが知られている。本研究成果は、瘢痕組織形成の抑制・減少を可能にすることで先に述べた現象を最小限に抑えることを意味し、矯正歯科臨床に大きな飛躍をもたらすことになると考える。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Crosstalk between Fas and S1P1 signaling via NF-κB in osteoclasts controls bone destruction in the TMJ due to rheumatoid arthritis.2019

    • Author(s)
      Hutami I.R., Tanaka E., Izawa T.
    • Journal Title

      Japanese Dental Science Review

      Volume: 55 Issue: 1 Pages: 12-19

    • DOI

      10.1016/j.jdsr.2018.09.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential role of rebamipide in osteoclast differentiation and mandibular condylar cartilage homeostasis2018

    • Author(s)
      Izawa T., Hutami I.R., Tanaka E.
    • Journal Title

      Current Rheumatology Reviews

      Volume: 14 Issue: 1 Pages: 62-69

    • DOI

      10.2174/1573397113666171017113441

    • NAID

      120006711352

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fas/S1P1 crosstalk via NF-κB activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis.2017

    • Author(s)
      Hutami I.R., Izawa T., Mino-Oka A., Shinohara T., Mori H., Iwasa A.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 490 Issue: 4 Pages: 1274-1281

    • DOI

      10.1016/j.bbrc.2017.07.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of Fas and RANKL signaling in peripheral immune tolerance2017

    • Author(s)
      Izawa T., Arakaki R., Ishimaru N.
    • Journal Title

      Journal of Clinical & Cellular Immunology

      Volume: 8 Issue: 04 Pages: 512-512

    • DOI

      10.4172/2155-9899.1000512

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis2017

    • Author(s)
      Izawa T., Arakaki R., Ishimaru N.
    • Journal Title

      Journal of Cytokine Biology

      Volume: 2 Issue: 02 Pages: 114-114

    • DOI

      10.4172/2576-3881.1000114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Signal crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis2018

    • Author(s)
      Izawa T., Arakaki R., Ishimaru N.
    • Organizer
      IMMUNOLOGY 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低酸素応答遺伝子HIF-1alphaはM1/M2マクロファージのリプログラミングを介して口蓋創傷治癒を制御する2018

    • Author(s)
      Hutami IR., Izawa T., Tanaka E.
    • Organizer
      日本口蓋裂学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] AhRはRANK/c-Fosシグナル伝達経路を介して破骨細胞の分化を制御する2018

    • Author(s)
      井澤 俊、田中栄二
    • Organizer
      第4回日本骨免疫学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HIF-1alpha regulates the palatal wound healing through M1/M2 macrophage reprogramming2018

    • Author(s)
      Hutami IR., Mori H., Khurel-Ochir T., Mino A., Iwasa A., Tanaka E., Izawa T.
    • Organizer
      96th Genral Session & Exhibition of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 樹状細胞によるFas非依存的T細胞のアポトーシスがMRL/lprマウスにおける自己免疫性関節炎を制御する2018

    • Author(s)
      井澤 俊、田中栄二
    • Organizer
      日本骨代謝学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] AhRはRANK/c-Fosシグナル伝達経路を介して破骨細胞の分化を制御する2018

    • Author(s)
      井澤 俊
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fas/S1P1 crosstalk via NF-κB activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis2018

    • Author(s)
      Hutami IR., Tanaka E., Izawa T.
    • Organizer
      American Society for Bone and Mineral Research 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of p21 on the development of TMJ-OA2018

    • Author(s)
      Khurel-Ochir T., Izawa T., Mori H., Iwasa A., Hutami IR., Tanaka E.
    • Organizer
      The 77th Annual Meeting of the Japanese Orthodontic Society
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice2018

    • Author(s)
      Izawa T.
    • Organizer
      MBSJ 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] S1P1/Fas signal crosstalk via NF-κB activation in osteoclasts controls subchondral bone remodeling in murine arthritis2018

    • Author(s)
      Izawa T.
    • Organizer
      Proceedings of the Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核内受容体AhRはRANK/c-Fosシグナル伝達経路を介して破骨細胞の分化を制御する.2017

    • Author(s)
      井澤 俊、田中栄二、石丸直澄
    • Organizer
      日本骨代謝学会
    • Related Report
      2017 Research-status Report
  • [Presentation] The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiationvia the RANK/c-Fos signaling axis.2017

    • Author(s)
      Izawa T., Tanaka E., Ishimaru N.
    • Organizer
      ASBMR 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of hypoxia inducible factor-1 alpha in the palatal wound healing.2017

    • Author(s)
      Hutami IR., Izawa T., Iwasa A., Oka A., Khurelochir T., Mori H., Tanaka E.
    • Organizer
      The 75th JOS annual meeting
    • Related Report
      2017 Research-status Report
  • [Presentation] The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis.2017

    • Author(s)
      井澤 俊、新垣理恵子、田中栄二、石丸直澄
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis.2017

    • Author(s)
      Izawa T., Arakaki R., Tanaka E., Ishimaru N.
    • Organizer
      Proceedings of the Japanese Society for Immunology
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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