A ferret model demonstrates sustained fibrosis, restrictive physiology, and airway proximalization

Unlike rodents, ferrets have human-like distribution of submucosal glands expressing MUC5B, associated with idiopathic pulmonary fibrosis (IPF). We evaluated ferrets exposed to a single dose of bleomycin (5 U/kg) longitudinally, and found sustained restrictive physiology, increased opacification and fibrotic injury in the lungs through 22 weeks. Notably, these lungs had an aberrant "proximalization" repair phenotype indicated by increased proportion of smaller airways co-expressing club cell secretory protein and alpha-tubulin that was associated with extent of fibrotic injury. We also observed MUC5B-positive cystic structures in the distal lung suggestive of honeycombing, consistent with increase of MUC5B+ airways in combination with a size shift to smaller airways. We conclude that ferrets exhibit aberrant repair and pathologic features characteristic of human IPF, including proximalization of the distal airways that has not been recapitulated in rodents. Heightened MUC5B expression may play a key role in promoting airway remodeling and sustained lung injury in IPF.

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Publication Details

Journal
npj Regenerative Medicine
Published
2025-11-27
DOI
https://doi.org/10.1038/s41536-025-00436-9
Primary Topic
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Type
article
Field-Weighted Citation Impact
0.00

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article

A ferret model demonstrates sustained fibrosis, restrictive physiology, and airway proximalization

Steven M. Rowe, Janna Ren, D. Stanford, Jeremy B. Foote et al.
npj Regenerative Medicine
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
article

A ferret model demonstrates sustained fibrosis, restrictive physiology, and airway proximalization

Steven M. Rowe, Janna Ren, D. Stanford, Jeremy B. Foote, Kevin S. Harrod, J.E. Peabody Lever, Jeremie M. Lever, Scott E. Phillips, Sayan Bakshi, Nikoleta Pavelková, Jared P. Kennemur, L. Jones, Shah S. Hussain, Mason Weupe, Qian Li, Harrison Kim, Dezhi Wang, Javier Campos, Liping Tang, Kajal Jadhav
article en

Abstract

Unlike rodents, ferrets have human-like distribution of submucosal glands expressing MUC5B, associated with idiopathic pulmonary fibrosis (IPF). We evaluated ferrets exposed to a single dose of bleomycin (5 U/kg) longitudinally, and found sustained restrictive physiology, increased opacification and fibrotic injury in the lungs through 22 weeks. Notably, these lungs had an aberrant "proximalization" repair phenotype indicated by increased proportion of smaller airways co-expressing club cell secretory protein and alpha-tubulin that was associated with extent of fibrotic injury. We also observed MUC5B-positive cystic structures in the distal lung suggestive of honeycombing, consistent with increase of MUC5B+ airways in combination with a size shift to smaller airways. We conclude that ferrets exhibit aberrant repair and pathologic features characteristic of human IPF, including proximalization of the distal airways that has not been recapitulated in rodents. Heightened MUC5B expression may play a key role in promoting airway remodeling and sustained lung injury in IPF.

npj Regenerative MedicineVol. 10(1)
University of Alabama at Birmingham (US)
National Institutes of Health, National Heart, Lung, and Blood Institute
Openalex Percentile: Top 45%
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
DOIOpen Access PDFOpenAlex
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