Abstract
The airway epithelium, a sophisticated multicellular layer lining the respiratory tract, serves as our first line of defense against pathogens, allergens, and environmental pollutants. Recent studies have illuminated the intricate interplay between basal cell self-renewal, differentiation, and epithelial homeostasis following injury. Notably, expression of caveolin-1 (Cav-1) has been linked to specific cell types within the airway epithelium, primarily basal stem cells (BSCs) and multiciliated cells (MCCs). Despite its specific expression, the precise function of Cav-1 in BSC differentiation remains largely enigmatic. In this study, we investigate Cav-1’s function within the airway epithelium in vitro, exploring the molecular mechanisms underlying BSC differentiation into MCCs and secretory cells (SCs). Our results reveal limited Cav-1 expression in mouse airway epithelial BSCs, with additional enrichment observed in MCCs. Notably, deficiency of Cav-1 accelerates MCC differentiation and maturation. Additionally, we found that Cav-1 downregulation dramatically affects Notch intracellular domain (NICD) transcriptional activity. That leads us to propose that Cav-1 participates indirectly in a transcriptional program orchestrated by NICD, thereby modulating both BSC differentiation and MCC maturation.
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Data availability
Data generated from NICD ChIP-seq experiments are deposited in the open-access repository Figshare (https://doi.org/10.6084/m9.figshare.31089241). Similarly, the RNA-seq data are available through Zenodo, a European Open Research Repository (https://doi.org/10.5281/zenodo.18303253).
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Acknowledgements
Confocal microscopy and scanning electron microscopy were performed at the UEX microscopy core facilities. This work was supported by TED2021-130560B-I00, PID2021-126905NB-I00, and PID2024-159320NB-I00 grants from the Ministry of Economy, IB24150 from Junta de Extremadura to J.M. C-G and GR24138 from Junta de Extremadura to S.M-N. This study was also supported by grants to M.A.d.P. from the Spanish Ministry of Science and Innovation (MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ARDF/FEDER) “A way to make Europe” PID2020-118658RB-I00 and PDC2021-121572-I00, and Fundación Obra Social La Caixa (AtheroConvergence, HR20-00075. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation) and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). S.G-J. was a recipient of a Fellowship from the Universidad de Extremadura. S. D-Ch and C.M.N-Q were recipients of a Fellowship from Junta de Extremadura. All Spanish funding is co-sponsored by the European Union FEDER program.
Funding
This work was supported by TED2021-130560B-I00, PID2021-126905NB-I00, and PID2024-159320NB-I00 grants from the Ministry of Economy, IB24150 from Junta de Extremadura to J.M. C-G and GR24138 from Junta de Extremadura to S.M-N. This study was also supported by grants to M.A.d.P. from the Spanish Ministry of Science and Innovation (MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ARDF/FEDER) “A way to make Europe” PID2020-118658RB-I00 and PDC2021-121572-I00, and Fundación Obra Social La Caixa (AtheroConvergence, HR20-00075. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation) and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/https://doi.org/10.13039/501100011033). All Spanish funding is co-sponsored by the European Union FEDER program. All Spanish funding is co-sponsored by the European Union FEDER program.
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M.O-G, G. C-L, J.F. B-L, N. D-D, A. D-P, M T-D, and M. C-M performed all of the experiments. G. C-L. and D.A.B. designed and performed the data analysis. S.M-N, A.C. C, M. D and J.M.C.-G. designed the experiments, analyzed data and wrote the manuscript.
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Olivera-Gómez, M., Cumplido-Laso, G., Benitez, D.A. et al. Caveolin-1 modulates Notch transcriptional activity during in vitro respiratory multiciliated cell maturation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40201-6
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DOI: https://doi.org/10.1038/s41598-026-40201-6
