Journal Article

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

Ren, Janna Q., Peabody Lever, Jacelyn E., Jones, Luke I., Phillips, Scott E., Weupe, Mason, Stanford, Denise D., Wang, Dezhi, Pavelkova, Nikoleta, Harrod, Kevin S., Li, Qian, Peabody Lever, Jeremie M., Hussain, Shah S., Jadhav, Kajal, Campos-Gomez, Javier, Kennemur, Jared P., Tang, Liping, Kim, Harrison, Bakshi, Sayan, Foote, Jeremy B., Rowe, Steven M.

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/80/304 / 692/699/1785 / Biomaterials / Biomedical and Life Sciences / Biomedicine / Cell Biology / Chronic obstructive pulmonary disease / Compliance / Females / Immunology / Lung diseases / Males / Mortality / Physiology / Pulmonary fibrosis / Pulse oximetry / Regenerative Medicine/Tissue Engineering / Stem Cells