High-resolution multimodal imaging reveals spatial and temporal heterogeneity of airway mucus plugging in mice with muco-obstructive lung disease
Mucus plugging is a hallmark of muco-obstructive lung diseases; however, the spatiotemporal dynamics of plug formation remain poorly understood. We used a multimodal high-resolution imaging approach to study mucus plugging in newborn (0-1 days), juvenile (13-16 days), and adult (49-59 days) βENaC-tr...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 November 2025
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| In: |
Scientific reports
Year: 2025, Volume: 15, Pages: 1-14 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-025-22537-7 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-025-22537-7 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-025-22537-7 
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| Author Notes: | Claudia V. Benke, Julia Duerr, Annika Engel, Christian Dullin, Wolfram Stiller, Heinz Horstmann, Claudia Redenbach, Maximilian Ackermann, Hans-Ulrich Kauczor, Thomas Kuner, Mark O. Wielpütz, Marcus A. Mall, and Willi L. Wagner |
| Summary: | Mucus plugging is a hallmark of muco-obstructive lung diseases; however, the spatiotemporal dynamics of plug formation remain poorly understood. We used a multimodal high-resolution imaging approach to study mucus plugging in newborn (0-1 days), juvenile (13-16 days), and adult (49-59 days) βENaC-transgenic mice (βENaC-tg, n = 24), a model of muco-obstructive lung disease, in comparison to age-matched wild-type mice (n = 28). Micro-computed tomography (µCT) enabled whole lung mucus scoring on a scale from 0 (no obstruction) to 2 (> 50% obstruction) using an extended murine airway tree nomenclature. A subset of βENaC-tg lungs (5 juvenile, 5 adult) underwent localised synchrotron radiation-based computed tomography (SRCT) for segmentation-based calculation of mucus area and contact ratios as indicators of luminal obstruction and airway wall adherence. µCT-guided scanning electron microscopy (SEM) provided nanoscale visualisation of mucus plugs on selected βENaC-tg lung samples (3 juvenile). µCT revealed age-dependent, heterogeneous mucus plug formation, with significantly increased mucus scores in juvenile (0.45 ± 0.26) and adult (0.30 ± 0.17) βENaC-tg compared to wild-type mice (0.01 ± 0.02 with P < 0.01, and 0.01 ± 0.02 with P < 0.05, respectively). SRCT analysis showed a strong positive correlation between mucus area and contact ratios (r ≥ 0.80), while SEM revealed the mucus plug ultrastructure. This multimodal imaging approach highlights the spatiotemporal heterogeneity of mucus plugging, forming a basis for future research on targeted therapeutic strategies for muco-obstructive lung diseases. |
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| Item Description: | Gesehen am 10.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-025-22537-7 |