Regulation of airway cartilage and smooth muscle balance by epithelial cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08208
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Yokohama City University
• Principal Investigator: Tadokoro Tomomi 横浜市立大学, 医学部, 助教 (20507644)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 上皮間葉相互作用 / 気道上皮幹細胞 / 気道軟骨 / 気道平滑筋

Outline of Final Research Achievements

The outside of the airway is composed of a combination of cartilage and smooth muscle, which maintains the strength of the airway and allows for the regulation of the airway's thickness. We revealed the spatial heterogeneity in airway basal stem cells and suggested their roles in airway development and maintenance (Tadokoro et al., Biol Open, 2021). Among the genes expressed by basal stem cells, Conditional knockout mice (cKO) were generated by crossing airway epithelial-specific Cre mice with Mstn flox mice. Using these cKO mice, we investigated the role of this gene in airway cartilage and smooth muscle formation. The results showed that airway cartilage was dysplastic in Mstn cKO mice and an increase in the distance between the C-rings of the airway cartilage was evident. A significant increase in smooth muscle width was observed. In conclusion, we revealed a regulatory mechanism of airway formation by epithelial-mesenchymal interactions.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により気道上皮細胞からのシグナルによる気道軟骨/気道平滑筋の分化調節メカニズムの一部について明らかにすることができた。気管間葉系の維持機構の破綻は、気管軟化症などで見られる軟骨の強度低下や、喘息などで見られる平滑筋量の増加または平滑筋の収縮制御異常などが挙げられ、気道の適切な構造が保てずに気管の狭窄が生じる。本研究の成果を活かすことにより、将来的に上記病態の改善や気道の再構成の実現が期待される。