Semin Respir Crit Care Med
DOI: 10.1055/a-2649-9402
Patricia Brazee
1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Center for
Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts
,
Nancy Allen
2
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine,
University of California San Francisco, San Francisco, California
,
Rachel Knipe
1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Center for
Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts
,
Elizabeth F. Redente
3
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver,
Colorado
,
Claude Jourdan Le Saux
2
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine,
University of California San Francisco, San Francisco, California
› Author AffiliationsFunding This study was funded by the California Institute for Regenerative Medicine (grant
no.: DISC0-13788) and U.S. Department of Health and Human Services, National Institutes
of Health, National Heart, Lung, and Blood Institute (grant nos.: K01HL174822 [P.B.],
K08HL169723 [N.A.], R01 HL168138 [R.K.], R35HL150767 [C.J.L.S.], RO1 HL147860 [E.R.],
RO1 HL149741[E.R.], RO1 HL166250 [E.R.], and U01HL134766 [C.J.L.S.].
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Abstract
Bleomycin-induced lung injury remains the most widely used and well-characterized
experimental model for studying pulmonary fibrosis, particularly idiopathic pulmonary
fibrosis (IPF). This review provides a comprehensive analysis of the bleomycin model's
utility, phases, variability, and translational relevance. Bleomycin administration
in rodents induces acute epithelial injury followed by inflammation, fibroblast activation,
extracellular matrix deposition, and eventual fibrosis. The model progresses through
defined stages, acute inflammation (days 1–7), fibrogenesis (days 7–28), and in most
cases, spontaneous resolution (days 42–63), making it suitable for understanding temporal
aspects of fibrosis and repair, the cell populations involved, and the signaling mechanisms
involved. Despite its advantages, the single-dose model lacks key features of human
IPF, including persistent fibrosis, honeycomb cysts, and fibroblastic foci. Repetitive
dosing and the use of aged mice have improved chronicity and recapitulation of progressive
disease and observation of the expansion of aberrant epithelial cell populations in
simple cyst structures. This review discusses route-specific effects, strain and sex
susceptibilities, and the growing role of microbiome and genetic background in influencing
fibrosis outcomes. It also highlights cellular responses across epithelial cell populations,
fibroblasts, endothelial cells, and immune cell populations. Although limitations
exist in this model—such as reversibility and incomplete modeling of human pathology—bleomycin
remains invaluable for mechanistic studies and preclinical drug screening. Importantly,
all FDA-approved antifibrotic drugs demonstrated efficacy in bleomycin models prior
to clinical success. The review advocates for careful model selection, incorporation
of persistent fibrosis models, and parallel use of human-relevant systems to enhance
translational relevance in pulmonary fibrosis research.
Keywords
mouse model -
pulmonary fibrosis -
bleomycin
Publication History
Article published online:
13 August 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
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