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responsiveness of nasal ciliated cell for extra- or intracellular ionic environmental change

Research Project

Project/Area Number 18K09325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Yasuda Makoto  京都府立医科大学, 医学(系)研究科(研究院), 講師 (60433273)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords線毛運動 / 鼻粘膜上皮細胞 / 細胞内イオン環境 / 細胞内クロライドイオン濃度 / CBF / CBA / 鼻粘膜上皮培養細胞 / 細胞内クロライド / 細胞内外環境 / 細胞内PH / 細胞内PH / 上下気道 / 鼻粘膜 / 培養細胞 / カルシウムイオン / クロライドイオン / 鼻粘膜上皮 / 線毛細胞 / イオン環境
Outline of Final Research Achievements

The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl-), and is enhanced by a decreased concentration of intracellular Cl- ([Cl-]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD)in cHNECs has been developed, which revealed that a decrease in [Cl-]i increased CBD, but not CBF, and an increase in [Cl-]i decreased both CBD and CBF. Thus, [Cl-]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl- sensors and be regulated by [Cl-]i. These observations indicate that the activation of Cl- secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl-]i in cHNECs. Thus, [Cl-]i is critical for controlling ciliary beating in cHNECs.

Academic Significance and Societal Importance of the Research Achievements

線毛運動は健全な鼻粘膜線毛輸送系を担う重要な細胞である。また線毛細胞を標的にした治療法はいまだにほとんど開発されておらず、未開拓の分野である。今回我々は細胞内クロライドイオン濃度の変化で線毛運動が変化することを示した。この制御機構をさらに詳細に研究することにより線毛運動の制御機構が明らかにできる。また細胞内クロライドイオンの低下を来たす薬剤を開発することにより線毛運動を活性化できる可能性が示唆された。慢性副鼻腔炎やアレルギー性鼻炎などの上気道炎症性疾患における今後の新たな薬剤開発のターゲットの一つになりうると考えられる。

Report

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

    (9 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (4 results)

  • [Journal Article] Intracellular Cl- Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy2020

    • Author(s)
      Yasuda M, Inui TA, Hirano S, Asano S, Okazaki T, Inui T, MARUNAKA Y, Nakahari T
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 11 Pages: 4052-4052

    • DOI

      10.3390/ijms21114052

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ciliary beating amplitude controlled by intracellular Cl- and a high rate of CO2 production in ciliated human nasal epithelial cells.2019

    • Author(s)
      Inui Taka‐aki、Murakami Kentaro, Yasuda Makoto、Hirano Shigeru、Ikeuchi Yukiko、Kogiso Haruka、Hosogi Shigekuni, Inui Toshio、Marunaka Yoshinori、Nakahari Takashi
    • Journal Title

      Pflugers Archiv - European Journal of Physiology

      Volume: 471 Issue: 3 Pages: 1127-1142

    • DOI

      10.1016/j.ymgme.2018.11.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells2019

    • Author(s)
      Inui Taka‐aki、Yasuda Makoto、Hirano Shigeru、Ikeuchi Yukiko、Kogiso Haruka、Inui Toshio、Marunaka Yoshinori、Nakahari Takashi
    • Journal Title

      The Laryngoscope

      Volume: - Issue: 5

    • DOI

      10.1002/lary.28185

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spontaneous oscillation of the ciliary beat frequency regulated by release of Ca2+ from intracellular stores in mouse nasal epithelia2018

    • Author(s)
      Kuremoto Toshihiro、Kogiso Haruka、Yasuda Makoto、Inui Taka-aki、Murakami Kentaro、Hirano Shigeru、Ikeuchi Yukiko、Hosogi Shigekuni、Inui Toshio、Marunaka Yoshinori、Nakahari Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 507 Issue: 1-4 Pages: 211-216

    • DOI

      10.1016/j.bbrc.2018.11.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl?]i Decrease in Ciliated Human Nasal Epithelial Cells2018

    • Author(s)
      Inui Taka-aki、Yasuda Makoto、Hirano Shigeru、Ikeuchi Yukiko、Kogiso Haruka、Inui Toshio、Marunaka Yoshinori、Nakahari Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 12 Pages: 3754-3754

    • DOI

      10.3390/ijms19123754

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ダイゼインの細胞内Cl濃度減少を介したヒト鼻粘膜培養細胞における線毛運動振幅の増加.2019

    • Author(s)
      乾 隆昭、平野 滋、安田 誠
    • Organizer
      第58回日本鼻科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 細胞内Cl-濃度依存的ヒト鼻粘膜線毛運動2018

    • Author(s)
      村上賢太郎、乾 隆昭、細木誠之、中張隆司、丸中良典、平野 滋、安田 誠
    • Organizer
      第36回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト鼻粘膜線毛細胞における振動数・振幅の測定法:[Cl-]iによる振幅調整2018

    • Author(s)
      乾 隆昭、村上賢太郎、細木誠之、中張隆司、丸中良典、平野 滋、安田 誠
    • Organizer
      第125回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞内カルシウムによるマウス鼻粘膜線毛運動の制御機構2018

    • Author(s)
      安田 誠、呉本年弘、村上賢太郎、乾 隆昭、平野 滋
    • Organizer
      第57回日本鼻科学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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