ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
Modeling pulmonary fibrosis through bleomycin delivered by osmotic minipump: a new histomorphometric method of evaluation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Myeloperoxidase promotes fibrosis by inhibiting cathepsin K to bias the lung toward ECM accumulation.bioRxiv : the preprint server for biology · 2026Article
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- In Vivo Target Engagement Assessment of Nintedanib in a Double-Hit Bleomycin Lung Fibrosis Rat Model.International journal of molecular sciences · 2025Article
- CD45+/ Col I+ Fibrocytes: Major source of collagen in the fibrotic lung, but not in passaged fibroblast cultures.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Article
- A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.American journal of physiology. Lung cellular and molecular physiology · 2024Article
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- Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.Nature communications · 2024Article
- Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model.International journal of molecular sciences · 2023Article
- Evaluation of renal damage in a bleomycin-induced murine model of systemic sclerosis.Iranian journal of basic medical sciences · 2023Article
- 3'5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.International journal of molecular sciences · 2022Article
- Nuclear respiratory factor-1 negatively regulates TGF-β1 and attenuates pulmonary fibrosis.iScience · 2022Article
- Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration.PloS one · 2022Article
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- Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening.PloS one · 2022Article
- SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib.Scientific reports · 2021Article
- Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary FibroblastsFrontiers in immunology · 2021Article
- Therapeutic Effect of Neuraminidase-1-Selective Inhibition in Mouse Models of Bleomycin-Induced Pulmonary Inflammation and Fibrosis.The Journal of pharmacology and experimental therapeutics · 2021Article
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9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The systemic delivery of bleomycin (BLM) to mice through subcutaneously implanted osmotic minipumps may be used to experimentally mimic the typical features of systemic sclerosis and related interstitial lung diseases. The published studies on this model principally have focused on induced dermal modifications, probably because lung lesions are typically mild, subpleurally localized, and difficult to analyze. The use of high BLM doses to increase their severity has been proposed but is ethically questionable because of the compromising of animal welfare. We propose a tailored histomorphometric method suitable to detect and quantify this type of mild lung lesions. Using a two-step automated image analysis, a peripheral region of interest with a depth of 250 µm from the pleural edge was defined on whole slide images, and the fibrotic foci were histomorphometrically characterized. The effects of different BLM doses on lung alterations were evaluated in C57BL/6 mice and 60 U/kg resulted in a fair compromise between fibrotic lesions and animal welfare. This dose was also tested in time course experiments. The analysis revealed a peak of histological fibrotic-like alterations, cytokine expression, metalloprotease, and macrophagic activation between the 21st and 28th day after pump implant. The induced dermal fibrosis was characterized by the progressive loss of the white dermal adipose layer, an increase in dermal thickness, dermal hyperplasia, and more compacted collagen fibers. Despite the trend toward spontaneous resolution, our model allowed a double organ readout of the BLM effect and the identification of a therapeutic window for testing pharmacological compounds without using life-threatening doses.
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