ArticleBMJ open respiratory research2023
Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes.
Article in BMJ open respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Modulatory effects of CeOParticle and fibre toxicology · 2026Article
- In Vivo Target Engagement Assessment of Nintedanib in a Double-Hit Bleomycin Lung Fibrosis Rat Model.International journal of molecular sciences · 2025Article
- Distinct lung functional, histological and cell senescence signatures in the single and repetitive bleomycin mouse models of idiopathic pulmonary fibrosis.Physiological reports · 2025Article
- Identification of the role ofJournal of thoracic disease · 2025Article
- 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
- Bifurcation in the healing or fibrotic response in a network model of fibrosis: role of the initial injury structure.Frontiers in network physiology · 2025Article
- Comparison of the Results of Modeling Pulmonary Fibrosis in Sprague Dawley Rats by Intratracheal Administration of Bleomycin in the Form of Sulfate and Chloride at a Dose of 3 mg/kg.Pharmaceuticals (Basel, Switzerland) · 2024Article
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Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential. The bleomycin (BLM) intratracheal murine model is the most commonly used preclinical assay to evaluate new potential therapies for IPF. Here, we present the findings derived from an integrated histomorphometric and transcriptomic analysis to investigate the development of lung fibrosis in a time-course study in a BLM rat model and to evaluate its translational value in relation to IPF.
methodsRats were intratracheally injected with a double dose of BLM (days 0-4) and sacrificed at days 7, 14, 21, 28 and 56. Histomorphometric analysis of lung fibrosis was performed on left lung sections. Transcriptome profiling by RNAseq was performed on the right lung lobes and results were compared with nine independent human gene-expression IPF studies.
resultsThe histomorphometric and transcriptomic analyses provided a detailed overview in terms of temporal gene-expression regulation during the establishment and repair of the fibrotic lesions. Moreover, the transcriptomic analysis identified three clusters of differentially coregulated genes whose expression was modulated in a time-dependent manner in response to BLM. One of these clusters, centred on extracellular matrix (ECM)-related process, was significantly correlated with histological parameters and gene sets derived from human IPF studies.
conclusionsThe model of lung fibrosis presented in this study lends itself as a valuable tool for preclinical efficacy evaluation of new potential drug candidates. The main finding was the identification of a group of persistently dysregulated genes, mostly related to ECM homoeostasis, which are shared with human IPF.
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