ArticleInternational journal of molecular sciences2024
Highly Calibrated Relationship Between Bleomycin Concentrations and Facets of the Active Phase Fibrosis in Classical Mouse Bleomycin Model.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Broad-Spectrum Protective Effects of Lyophilized FE002-Lu Lung Fibroblast Conditioned Medium Against Acute and Chronic Pulmonary Injury in Wistar Rats.Biomedicines · 2026Article
- A novel two-hit murine model of inhaled occupational exposure-induced lung disease.Physiological reports · 2026Article
- Inhibition of runt related transcription factor 1 with Ro24-7429 improves lung function in experimental models of idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- Development of a translational murine model for antibody-drug conjugate-induced interstitial lung disease.NPJ precision oncology · 2026Article
- Interobserver Variability and Histopathologic Correlation of Lung Ultrasonography in a Bleomycin-Induced Mouse Model of Systemic Sclerosis.Biomedicines · 2026Article
- The IL-33-ILC2 axis: a key regulator of type 2 immunity in respiratory disease.Frontiers in immunology · 2026Review
- Different degrees of expression of pulmonary fibrosis signs with intratracheal administration of bleomycin at different doses in male SD rats (a study aimed at helping to select the optimal bleomycin dose for modeling pulmonary fibrosis).Frontiers in pharmacology · 2025Article
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Abstract
The mouse bleomycin model is useful in pre-clinical IPF research to understand pathophysiological mechanisms and pharmacological interventions. In the present study, we systematically investigated the effects of bleomycin at a 60-fold dose range on experimental features of lung fibrosis in the mouse bleomycin model. We analyzed the effect of intratracheal (i.t.) dosing of 0.05-3 U/kg bleomycin on disease phenotypes, including weight loss, morbidity and mortality, pulmonary inflammation, lung collagen content, various BALF biomarkers, and histology in a 14-day mouse model when the animals are in the active phase of fibrosis. In mice, challenge with 1-2 U/kg bleomycin doses induced significant and saturated responses on fibrotic endpoints, confirmed by collagen content, BALF biomarker levels, and marked weight loss compared to the normal control (NC). We observed 100% mortality in 3 U/kg of bleomycin-treated mice. In contrast, 0.05-0.5 U/kg bleomycin doses induced a dose-dependent fibrotic phenotype. The mice challenged with doses of 0.25-0.5 U/kg bleomycin showed optimum body weight loss, a significant increase in pulmonary inflammation, and the fibrotic phenotype compared to NC. Furthermore, we showed 0.25-0.5 U/kg bleomycin increases expression levels of (pro-) fibrotic cytokines, which are the mediators involved in the activation of myofibroblast during fibrogenesis (TGF-β1, IL-13, IL-6, WISP-1, VEGF), angiogenesis (VEGF), matrix remodeling (TIMP-1), and non-invasive lung function biomarker (CRP) compared to NC. A modified Ashcroft scale quantified that the fibrotic changes in the lungs were significantly higher in the lung of mice dosed at 0.25-0.5 U/kg > 0.1 U/kg bleomycin and non-significant in mice lung dosed at 0.05 U/kg bleomycin compared to NC. We demonstrated that the changes due to 0.25-0.5 U/kg i.t. bleomycin on protein biomarkers are enough to drive robust and detectable fibrotic pathology without mortality. The 0.1 U/kg has a moderate phenotype, and 0.05 U/kg had no detectable phenotype. The Goodness of Fit (
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