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Elucidation of the mechanism of compensatory hyperfunction of salivary glands and induction of enhancement of secretion using in vivo functional analysis.

Research Project

Project/Area Number 20K09882
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

Nezu Akihiro  北海道医療大学, 歯学部, 准教授 (00305913)

Co-Investigator(Kenkyū-buntansha) 森田 貴雄  日本歯科大学, 新潟生命歯学部, 教授 (20326549)
細矢 明宏  北海道医療大学, 歯学部, 教授 (70350824)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords唾液分泌 / 代償性肥大 / 機能亢進 / Ca2+応答 / in vivo機能解析 / 網羅的遺伝子解析 / in vivo機能解析法 / 代償性機能亢進 / 細胞内カルシウム応答 / 腺血流 / 機能亢進腺 / 細胞内カルシウム動態 / 遺伝子発現 / in vivo 機能解析 / 代償性機能亢進機構 / 遺伝子発現解析 / Ca2+イメージング / 血流動態 / In vivo機能解析
Outline of Research at the Start

唾液腺は片側が機能不全に陥ると残った唾液腺が代償性に肥大し、低下した唾液分泌を補っている。本研究課題では片側唾液腺障害によって起こる唾液腺の代償性機能亢進を起こすしくみを明らかにすることを目的とする。本目的を達成するため、①「機能亢進腺」の遺伝子発現量および局在解析と②「機能亢進腺」におけるintravital イメージングおよび唾液分泌の同時測定によるin vivo機能解析法を用いて、機能亢進を誘導する神経伝達物質や内因性シグナル分子を解析する。また網羅的遺伝子解析により得られた「機能亢進腺」で変化する遺伝子を検索し、そのしくみを利用した「唾液が出やすくなる唾液腺」の誘導を試みる。

Outline of Final Research Achievements

When one side of the salivary gland is dysfunctional, the remaining gland compensates for the low salivary secretion by compensatory hypertrophy. By simultaneously monitoring the Ca2+ response and salivary secretion of the submandibular gland in living animals, we have shown that signals causing compensatory hypertrophy induce the remaining submandibular gland to become a hyperfunctioning gland. Comprehensive gene analysis of submandibular gland tissue identified 6 marker genes associated with hyperfunctioning glands. Furthermore, the quantitative analysis of these marker genes changes revealed the involvement of parasympathetic nervous system transmitters as signals for induction of this hyperfunction due to the unilateral submandibular glands dysfunction. Measurement of the number of cell growth factor-positive cells suggested that differentiation from ductal cells to acinar cells and proliferation of acinar cells were occurring in the hyperfunctioning glands.

Academic Significance and Societal Importance of the Research Achievements

本課題では、唾液腺のCa2+応答と唾液分泌を同時に測定可能なin vivo機能解析法を用いて、唾液腺の代償性肥大は単なる腺肥大ではなく分泌刺激に対する感受性が亢進した機能亢進腺へ誘導することを明らかにした。また機能亢進腺の網羅的遺伝子変動解析により、機能亢進腺で変化するマーカー遺伝子を同定し、それらを用いて副交感神経系伝達物質が誘導シグナルとして働くことを示した。さらにマーカー遺伝子変動や増殖因子の陽性細胞数計測により、このシグナルは導管から腺房へ分化と細胞増殖に関与する可能性が示された。得られた知見は、生体が持つ自己回復能の誘導による全く新しいドライマウス治療法への応用が期待できる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (32 results)

All 2024 2023 2022 2021 2020

All Journal Article (9 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (23 results)

  • [Journal Article] Local anesthetics inhibit muscarinic acetylcholine receptor-mediated calcium responses and the recruitment of β-arrestin in HSY human parotid cells2024

    • Author(s)
      Shimatani Mari、Morita Takao、Yanuar Rezon、Nezu Akihiro、Tanimura Akihiko
    • Journal Title

      Journal of Oral Biosciences

      Volume: - Issue: 2 Pages: 465-472

    • DOI

      10.1016/j.job.2024.04.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Muscarinic acetylcholine receptor-mediated phosphorylation of extracellular signal-regulated kinase in HSY salivary ductal cells involves distinct signaling pathways2024

    • Author(s)
      Yanuar Rezon、Semba Shingo、Nezu Akihiro、Tanimura Akihiko
    • Journal Title

      Journal of Oral Biosciences

      Volume: - Issue: 2 Pages: 447-455

    • DOI

      10.1016/j.job.2024.02.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of aquaporin 5 and glandular blood flow in the acetylcholine-induced secretion of saliva in rats2023

    • Author(s)
      AKTER MST Tahmina、NEZU Akihiro、AKAMATSU Tetsuya、TANIMURA Akihiko
    • Journal Title

      Biomedical Research

      Volume: 44 Issue: 2 Pages: 51-63

    • DOI

      10.2220/biomedres.44.51

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2023-04-02
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of receptor‐mediated calcium responses by phenytoin through the suppression of calcium excretion in human gingival fibroblasts2023

    • Author(s)
      Minowa Erika、Hayashi Yoshinobu、Goh Kenji、Ishida Narumi、Kurashige Yoshihito、Nezu Akihiro、Saitoh Masato、Tanimura Akihiko
    • Journal Title

      Journal of Periodontal Research

      Volume: 58 Issue: 2 Pages: 274-282

    • DOI

      10.1111/jre.13089

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insertion of circularly permuted cyan fluorescent protein into the ligand-binding domain of inositol 1,4,5-trisphosphate receptor for enhanced FRET upon binding of fluorescent ligand2022

    • Author(s)
      Jahan Azmeree、Akter MST Tahmina、Takemoto Kiwamu、Oura Tai、Shitara Akiko、Semba Shingo、Nezu Akihiro、Suto Satoshi、Nagai Takeharu、Tanimura Akihiko
    • Journal Title

      Cell Calcium

      Volume: 108 Pages: 102668-102668

    • DOI

      10.1016/j.ceca.2022.102668

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent findings on the therapeutic effect of pilocarpine on dry mouth.2022

    • Author(s)
      MST. Tahmina Akter, Akihiro Nezu Akihiko Tanimura.
    • Journal Title

      北海道医療大学歯学会雑誌

      Volume: 41 Pages: 27-28

    • Related Report
      2022 Research-status Report
  • [Journal Article] Responses of salivary glands to intake of soft diet2022

    • Author(s)
      Takahashi Shigeru、Nezu Akihiro、Tanimura Akihiko、Nakamichi Yoshiyuki、Yamamoto Tsuneyuki
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 2 Pages: 210-216

    • DOI

      10.1016/j.job.2022.03.006

    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Journal Article] Spontaneous calcium responses of SF2 rat dental epithelial cells stably expressing the calcium sensor G-GECO2021

    • Author(s)
      ISHIDA Narumi、MURATA Kaori、MORITA Takao、SEMBA Shingo、NEZU Akihiro、TANIMURA Akihiko
    • Journal Title

      Biomedical Research

      Volume: 42 Issue: 5 Pages: 193-201

    • DOI

      10.2220/biomedres.42.193

    • NAID

      130008090720

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2021-09-21
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 「どのくらいの細胞内Ca2+濃度上昇で唾液分泌は起こるのか?」2020

    • Author(s)
      根津顕弘,谷村明彦.
    • Journal Title

      北海道医療大学歯学雑誌

      Volume: 39 Pages: 43-43

    • NAID

      120006884799

    • Related Report
      2020 Research-status Report
  • [Presentation] 固形餌の咀嚼による唾液腺の機能維持と自己回復における神経系の関与2024

    • Author(s)
      根津顕弘、藤田尚正、照光 真、谷村明彦
    • Organizer
      北海道医療大学歯学会第42回学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔感覚刺激による唾液腺の自己回復機構の解析2023

    • Author(s)
      根津顕弘、高橋 茂、加藤志織、谷村明彦
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔感覚刺激による唾液腺の自己回復メカニズムの解明2023

    • Author(s)
      根津顕弘、高橋 茂、加藤志織、谷村明彦
    • Organizer
      第67回日本唾液腺学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔感覚刺激を介した唾液腺の自己回復のしくみの薬理学的解析2023

    • Author(s)
      根津顕弘、高橋 茂、加藤志織、谷村明彦
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] AQP5レベルの異なるラット系統を用いた唾液分泌機構の薬理学的解析2022

    • Author(s)
      根津顕弘、MST Tahmina Akter、谷村明彦
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Carbachol and Pilocarpine activate ERK signaling via distinct mechanism.2022

    • Author(s)
      2.Rezon Yanuar, Shingo Semba, Akihiro Nezu, Takao Morita and Akihiko Tanimura.
    • Organizer
      第66回日本唾液腺学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] アセチルコリン刺激による顎下腺全体で起こるCa2+オシレーションと血流振動の制御メカニズム2022

    • Author(s)
      根津顕弘, 森田貴雄, 石井久淑, 谷村明彦
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Role of blood flow changes on acetylcholine-induced salivary secretion in rat strains with different level of aquaporin 5.2022

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 骨の透明化技術とイメージングによる扁平上皮癌細胞の骨破壊と骨形成抑制の解析.2022

    • Author(s)
      島谷真梨, 根津顕弘, 谷村明彦
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Muscarinic receptor agonists activate ERK signaling via distinct mechanism in salivary cells.2022

    • Author(s)
      Rezon Yanuar, Shingo Semba, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第35回薬物作用談話会
    • Related Report
      2022 Research-status Report
  • [Presentation] ラット顎下腺におけるアセチルコリンによる組織全体の同期するCa2+オシレーションと血流変動の関係2022

    • Author(s)
      根津顕弘、森田貴雄、石井久淑、永井健治、谷村明彦
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Elucidation of salivary secretion mechanism and development of novel treatments for dry mouth using different AQP5 expression rat strains.2021

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第34回北海道薬物作用談話会
    • Related Report
      2021 Research-status Report
  • [Presentation] Acetylcholine-induced blood flow changes play important role for salivary secretion in different AQP5 expression rat strains.2021

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] アセチルコリン刺激によって生じる顎下腺のCa2+と血流オシレーションとその調節機構.2021

    • Author(s)
      根津顕弘、森田貴雄、石井久淑、谷村明彦.
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 透明化技術を用いた扁平上皮癌細胞による骨破壊と骨形成抑制のイメージング解析.2021

    • Author(s)
      島谷真梨, 根津顕弘, 谷村明彦.
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Role of blood flow changes on acetylcholine-induced salivary secretion in rat strains differentially expressing AQP52021

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura
    • Organizer
      第65回日本唾液腺学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] アセチルコリン刺激により生じる顎下腺のCa2+オシレーションと血流振動の調節機構2021

    • Author(s)
      根津顕弘, 森田貴雄, 石井久淑, 谷村明彦
    • Organizer
      第65回日本唾液腺学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Intravital Ca2+ imagingと遺伝子解析による唾液腺における代償性機能亢進の分子機構の解明2021

    • Author(s)
      根津顕弘、高橋 茂、森田貴雄、谷村明彦
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Comparison of acetylcholine-induced salivary secretion in different AQP5 expression rat strains2021

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura
    • Organizer
      北海道医療大学歯学会第39回学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Intravital imagingと遺伝子解析による唾液腺における代償性機能亢進の分子機構の解明.2020

    • Author(s)
      根津顕弘,高橋 茂,森田貴雄,谷村明彦.
    • Organizer
      第62回歯科基礎医学会学位術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ラットグリア細胞腫瘍由来C6細胞のATP刺激による細胞体と突起部のカルシウム応答の特性.2020

    • Author(s)
      郷賢治,根津顕弘,照光真,谷村明彦.
    • Organizer
      第62回歯科基礎医学会学位術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Development of fluorescent biosensors using competitive FRET analyses.2020

    • Author(s)
      Azmeree Jahan, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第62回歯科基礎医学会学位術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Analysis of acetylcholine-induced salivary secretion in different AQP5 expression rat strains.2020

    • Author(s)
      Tahmina Akter, Akihiro Nezu, Akihiko Tanimura.
    • Organizer
      第62回歯科基礎医学会学位術大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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