Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis

Shuang Wu; Ian Driver; Meihui Luo; Hikaru Miyazaki; Smitha Shambhu; Dimitry Popov; Liyuan Yang; Jing Wang; Jia Ma; Junfeng Guo; Jarron Atha; Aleksandra Tata; Eric A Hoffman; Yujiong Wang; Purushothama Rao Tata; Martin B Jensen; John F Engelhardt; Vishwaraj Sontake; Xiaoming Liu

doi:10.1038/s41536-025-00440-z

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Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis

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Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis

Shuang Wu, Ian Driver, Meihui Luo, Hikaru Miyazaki, Smitha Shambhu, Dimitry Popov, Liyuan Yang, Jing Wang, Jia Ma, Junfeng Guo, …

npj Regenerative medicine, Vol.10(1), 53

11/21/2025

DOI: 10.1038/s41536-025-00440-z

PMCID: PMC12639051

PMID: 41271777

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options, partly due to a lack of effective disease models. This study presents a ferret model of pulmonary fibrosis (PF) induced by bleomycin, which replicates key characteristics of human IPF. The ferret model demonstrates an irreversible loss of pulmonary compliance, increased opacification, and structures resembling honeycomb cysts. Using single-nucleus RNA sequencing, we observed a significant shift in the distal lung epithelium toward a proximal phenotype. Cell trajectory analysis showed that AT2 cells transition into KRT8high/KRT7low/SOX4+ cells, and eventually into KRT8high/KRT7high/SFN+/TP63+/KRT5low “basaloid-like” cells. These cells, along with KRT7 and KRT8 populations, are located over myofibroblasts in fibrotic areas, suggesting a role in fibrosis progression similar to that in human IPF. This model accurately reproduces the pathophysiological and molecular features of human IPF, making it a valuable tool for future research and therapeutic development.

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Title: Subtitle: Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis
Creators: Shuang Wu - University of Iowa
Ian Driver - Gordian Biotechnology, South San Francisco, CA, USA
Meihui Luo - University of Iowa
Hikaru Miyazaki - Gordian Biotechnology, South San Francisco, CA, USA
Smitha Shambhu - Gordian Biotechnology, South San Francisco, CA, USA
Dimitry Popov - Gordian Biotechnology, South San Francisco, CA, USA
Liyuan Yang - University of Iowa
Jing Wang - Ningxia University
Jia Ma - University of Iowa
Junfeng Guo - University of Iowa
Jarron Atha - University of Iowa
Aleksandra Tata - Duke University
Eric A Hoffman - University of Iowa
Yujiong Wang - Ningxia University
Purushothama Rao Tata - Duke University
Martin B Jensen - Gordian Biotechnology, South San Francisco, CA, USA
John F Engelhardt - University of Alabama at Birmingham
Vishwaraj Sontake - Gordian Biotechnology, South San Francisco, CA, USA. vishwa@gordian.bio
Xiaoming Liu - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: npj Regenerative medicine, Vol.10(1), 53
DOI: 10.1038/s41536-025-00440-z
PMID: 41271777
PMCID: PMC12639051
NLM abbreviation: NPJ Regen Med
ISSN: 2057-3995
eISSN: 2057-3995
Publisher: Springer Nature
Grant note: 75N92024R00008 / National Institutes of Health NHLBI R01HL160939 / National Institutes of Health NHLBI
Language: English
Date published: 11/21/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Anatomy and Cell Biology; Internal Medicine
Record Identifier: 9985033764802771

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