Repeated instillations of bleomycin in male mice induce a perivascular remodeling at distance of fibrotic areas in the context of progressive pulmonary fibrosis
5 affiliations
- 1Laboratoire Hypoxie & Poumon, INSERM, U1272 Université Sorbonne Paris‐Nord Bobigny France
- 2Faculté de Médecine Sorbonne Université Paris France
- 3Service de Pneumologie, Hôpital Avicenne, APHP Bobigny France
- 4Service de Physiologie et d'Explorations Fonctionnelles, Hôpital Avicenne, APHP Bobigny France
- 5INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP Team Université Grenoble Alpes Grenoble France
Abstract
Idiopathic pulmonary fibrosis (IPF) is the archetypal form of progressive pulmonary fibrosis (PPF), as well as being the most common and severe type of interstitial lung disease. IPF is characterized by progressive, diffuse interstitial remodeling, stiffening of the lung parenchyma and is also most often associated with pulmonary hypertension (PH), which significantly impacts the clinical course and outcome of the disease. To improve targeted therapeutic options and survival predictions, as well as offering an overall better understanding of the disease, researchers need models that best reflect the characteristics observed in patients and allow the study of comorbidities associated with pulmonary fibrosis. Chronic pulmonary fibrosis was induced in male C57BL/6 mice through intratracheal instillation (ITI) of 3 low‐doses of bleomycin (BLM) every 2 weeks. Mice were sacrificed 15 or 90 days after the last ITI. Clinical follow‐up and histological analysis were performed to study lung and perivascular remodeling. Our results suggest that fractionated bleomycin instillation generates a persistent and progressive pulmonary fibrosis in mice. This is associated with collagen remodeling in the perivascular space outside fibrotic areas. We hypothesize that this remodeling, accompanied by a mild but significant increase in pulmonary artery media thickness, could be a precursor to pulmonary fibrosis‐associated hypertension. These results suggest that this model could improve our understanding of pulmonary remodeling and vascular lesions in the early stages of pulmonary fibrosis.
Related
- Triggering Receptor Expressed on Myeloid Cells‐2 Regulates Innate Lymphoid Cell Levels in Bleomycin‐Induced Pulmonary Fibrosis
- Blockade of the calpain-1/HSP90/TGF-β1 axis by Astragaloside IV ameliorates bleomycin-induced pulmonary fibrosis
- Proteomic Characterization of Prostate Cancer Bone Metastasis Subtypes Defines Progressive Remodeling States of the Bone-Tumor Microenvironment
- Progressive remodeling of global protein interaction networks in a mouse model of tauopathy
- Automated quantitative analysis can support the identification of progressive pulmonary fibrosis in fibrotic interstitial lung disease.
BibTeX
@article{yegen2026repeated,
title = {{Repeated instillations of bleomycin in male mice induce a perivascular remodeling at distance of fibrotic areas in the context of progressive pulmonary fibrosis}},
author = {Céline‐Hivda Yegen and Zakaria Maakoul and Dominique Marchant and Patrice Callard and Julia Bourse and Jean‐François Bernaudin and Hilario Nunes and Carole Planès and Emilie Boncoeur and Nicolas Voituron},
journal = {Animal Models and Experimental Medicine},
year = {2026},
month = sep,
doi = {10.1002/ame2.70247},
url = {https://doi.org/10.1002/ame2.70247},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Repeated instillations of bleomycin in male mice induce a perivascular remodeling at distance of fibrotic areas in the context of progressive pulmonary fibrosis
AU - Céline‐Hivda Yegen
AU - Zakaria Maakoul
AU - Dominique Marchant
AU - Patrice Callard
AU - Julia Bourse
AU - Jean‐François Bernaudin
AU - Hilario Nunes
AU - Carole Planès
AU - Emilie Boncoeur
AU - Nicolas Voituron
PY - 2026
DA - 2026/09/25
JO - Animal Models and Experimental Medicine
DO - 10.1002/ame2.70247
UR - https://doi.org/10.1002/ame2.70247
AB - Idiopathic pulmonary fibrosis (IPF) is the archetypal form of progressive pulmonary fibrosis (PPF), as well as being the most common and severe type of interstitial lung disease. IPF is characterized by progressive, diffuse interstitial remodeling, stiffening of the lung parenchyma and is also most often associated with pulmonary hypertension (PH), which significantly impacts the clinical course and outcome of the disease. To improve targeted therapeutic options and survival predictions, as well as offering an overall better understanding of the disease, researchers need models that best reflect the characteristics observed in patients and allow the study of comorbidities associated with pulmonary fibrosis. Chronic pulmonary fibrosis was induced in male C57BL/6 mice through intratracheal instillation (ITI) of 3 low‐doses of bleomycin (BLM) every 2 weeks. Mice were sacrificed 15 or 90 days after the last ITI. Clinical follow‐up and histological analysis were performed to study lung and perivascular remodeling. Our results suggest that fractionated bleomycin instillation generates a persistent and progressive pulmonary fibrosis in mice. This is associated with collagen remodeling in the perivascular space outside fibrotic areas. We hypothesize that this remodeling, accompanied by a mild but significant increase in pulmonary artery media thickness, could be a precursor to pulmonary fibrosis‐associated hypertension. These results suggest that this model could improve our understanding of pulmonary remodeling and vascular lesions in the early stages of pulmonary fibrosis.
SN - 2096-5451
SN - 2576-2095
ER -