2022 Fiscal Year Final Research Report
Regulation of the ciliary beat by intracellular Ca2+ oscillation in the nasal epithelial cells
| Project/Area Number |
19K09879
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大淵 豊明 産業医科大学, 医学部, 講師 (00412651)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 線毛運動 / 鼻粘膜 / 細胞内カルシウム / 単離線毛細胞 / Fluo-8 / 電位依存性カルシウムチャネル / TRPチャネル / オシレーション |
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| Outline of Final Research Achievements |
Mucociliary transport function plays an important role in the mucosal defense of the airway, and is largely depend on ciliary beating. This function is often impaired in various upper and lower airway diseases. In the present study, we investigated the regulatory mechanism of ciliary beating of the human nasal mucosa by means of ex vivo measurement of ciliary beat frequency/ATP release, immunohistochemistry, Western blot, immunoelectron microscopy, RT-PCR, and intracellular calcium imaging. Continuous increase in the intracellular calcium level induced by the Pannexin-1―P2X7 unit activates calmodulin, followed by the signaling cascade of adenylate/guanylate cyclases, cAMP/cGMP, and protein kinases A/G. The transmitted signal is then relayed to T-type voltage-gated calcium channel, which can generate intracellular calcium oscillation. A better understanding of the regulatory mechanism will be helpful in developing a new therapeutic strategy for intractable airway diseases.
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| Free Research Field |
耳鼻咽喉科
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| Academic Significance and Societal Importance of the Research Achievements |
気道上皮の線毛運動については、単細胞生物、実験動物、培養細胞を用いた研究がこれまでに行われてきたが、ヒトの組織や単離細胞を使った研究は非常に限られている。本研究では手術で切除した鼻粘膜およびそこから単離した細胞を、採取後2～3時間のうちにex vivoの状態で観察したため、ヒトのin vivoに近い現象の研究が可能となった。線毛運動の障害は種々の上気道・下気道疾患において認められ、気道上皮線毛運動の制御機構の解明は、難治性の上・下気道疾患に対する新たな治療法の開発に結び付くものと考えられる。本研究はこうした点で優れた学術的意義と社会的意義を有していると考えられる。
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