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Project description:Intratracheal application of bleomycin is known to induce inflammatory and fibrotic reactions in the lung within a short period of time and histological features include infiltration of inflammatory cells, collagen deposition and obliteration of alveolar spaces. Because some of these features are found in patients with idiopathic pulmonary fibrosis (IPF), the bleomycin-induced lung fibrosis animal model is commonly used. However, exploratory treatments that were successfully used in this animal model and progressed to clinical trials lacked significant efficacy in humans. Here, the bleomycin-induced rat lung fibrosis model was studied using whole genome expression data that was collected at various time points and the relevance to human disease was evaluated through comparison with whole genome expression data from IPF patient-derived lung biopsies. The highest gene expression correlation between both species was observed in animals 7 days after bleomycin instillation. These gene expression signatures helped to identify a set of twelve novel disease-relevant translational gene markers that were able to separate IPF patients from controls. Furthermore, three Wnt/-catenin pathway-related genes that belong to this translational gene marker set showed, together with clinical diffusing capacity of the lung for carbon monoxide (DLCO) measurements, the potential to stratify IPF patients according to disease severity. Pirfenidone attenuated a subset of the translational gene markers in the bleomycin-induced fibrosis model, in particular those related to Wnt/-catenin-signaling. This novel translational gene marker panel offers improved possibilities to evaluate disease-modifying efficacy of novel therapeutic concepts in the bleomycin-induced rat lung fibrosis model and could be applied as a diagnostic and prognostic tool for IPF patient care. Comparison of bleomycin-treated and control rats after 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks; 5 animals per group
2014-10-28 | E-GEOD-48455 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive disease leading to death with few effective treatments. Our previous study suggested that repetitive hyperbaric oxygen (HBO) treatment alleviates bleomycin-induced pulmonary fibrosis in mice, but the underlying mechanism is not clear. In this study, we compared the RNA-seq data from bleomycin challenged mouse lung tissues with or without repetitive HBO treatment, to figure out the affected biological processes and pathways. Combined with integrative analysis of public data from GEO, our study support HBO treatment as a viable strategy against pulmonary fibrosis.
2022-09-29 | GSE200109 | GEO
Project description:To understand the cellular composition and transcriptional phenotype of different cell populations in the mouse bleomycin induced fibrosis model, we performed RNAseq analysis on leukocyte, endothelial, epithelial and stroma (other) cell populations isolated from mouse lung samples.
2021-08-06 | GSE168529 | GEO
Project description:The molecular mechanisms of lung injury and fibrosis are incompletely understood. microRNAs (miRNAs) are crucial biological regulators by suppression of their target genes and are involved in a variety of pathophysiologic processes. To gain insight into miRNAs in the regulation of lung fibrosis, total RNA was isolated from lung samples harvested at different days after bleomycin treatment, and miRNA array was performed thereafter. miRNAs expressed in lungs with bleomycin treatment at different time points were compared to miRNAs expressed in lungs without bleomycin treatment, resulting in 161 miRNAs differentially expressed. Furthermore, miRNA expression patterns regulated in initial and late periods after bleomycin were identified. Target genes were predicted in silico for differentially expressed miRNAs, including miR-7f, miR-7g, miR-196b, miR-16, miR-195, miR-25, miR-144, miR-351, miR-34a, miR-499, miR-704, miR-717, miR-10a, miR-211, miR-34a, miR-367 and miR-21, and then cross-referenced to molecular pathways including apoptosis, Wnt, Toll-like receptor, and TGF-? signaling, which are involved in different pathological phenotypes such as apoptosis, inflammation, and fibrosis. Our study demonstrated relative abundance of miRNA levels in bleomycin-induced lung fibrosis. The miRNAs and their potential target genes identified herein contribute to the understanding of the complex transcriptional program of lung fibrosis. Under anesthesia, 2.5 U/kg bleomycin dissolved in sterile PBS was administered via trachea as previously described. Lung tissues were harvested at the time point of day 0, 3, 7, 14, and 21 post bleomycin challenges. 3 sample in specific time point, except for day 14 where nday14 = 2.
2012-04-12 | E-GEOD-24323 | biostudies-arrayexpress
Project description:Bleomycin-induced pulmonary fibrosis in mice mimics major hallmarks of idiopathic pulmonary fibrosis, yet in this model it spontaneously resolves over time. We studied molecular mechanisms of fibrosis resolution and lung repair, focusing on transcriptional and proteomic signatures and the effect of aging. Young (3 months) and old (21 months) mice were treated with Bleomycin or with control saline solution and analyzed transcript and protein expression over 8 weeks (Day 0, 14, 21, 28, 35, 42, 49, 56).
2023-08-09 | PXD041050 | Pride
Project description:Bleomycin-induced pulmonary fibrosis in mice mimics major hallmarks of idiopathic pulmonary fibrosis, yet in this model it spontaneously resolves over time. We studied molecular mechanisms of fibrosis resolution and lung repair, focusing on transcriptional and proteomic signatures and the effect of aging. Young (3 months) and old (21 months) mice were treated with Bleomycin or with control saline solution and analyzed transcript and protein expression over 8 weeks (Day 0, 14, 21, 28, 35, 42, 49, 56).
2024-09-10 | PXD040530 | Pride
Project description:The most preclinical used in vivo model to study lung fibrosis is the bleomycin-induced lung fibrosis model in 2-3-month-old mice. Although this model resembles key aspects of idiopathic pulmonary fibrosis (IPF), there are limitations in its predictability for the human disease. One of the main differences is the juvenile age of animals that are usually used in experiments, resembling humans of around 20 years. Because IPF patients are usually older than 60 years, aging appears to play an important role in the pathogenesis of lung fibrosis. We here compared young (3 months) and old (21 months) mice 21 days after intratracheal bleomycin instillation.
2024-09-10 | PXD026222 | Pride
Project description:Lung fibrosis represents the final common pathway of a variety of lung injuries, and it is characterized, independently of etiology, by the expansion of the fibroblast/myofibroblast population and by the abnormal accumulation of extracellular matrix (ECM) replacing normal functional parenchyma. In general, there is no effective therapy, and currently the only helpful available treatment for advanced lung fibrosis is transplantation. In this study we aimed to document the time-related reversibility of bleomycin-induced lung fibrosis, and to determine the gene expression patterns associated with the initial progression and the subsequent regression of the fibrotic response by microarray in this bleomycin mouse model of lung fibrosis. Mice (C57BL/6 ) aging 8 to 10 weeks were instilled intratracheally with 0.10 U/10 g of bleomycin (Blenoxane, Bristol-Myers Squibb Co.) in 50 μl sterile saline. Control animals received an equal volume of sterile saline (9, 10). Mice were housed in specific pathogen-free conditions and provided with food and water ad libitum. All studies and procedures were approved by the Science and Ethic Committee at the National Institute of Respiratory Diseases and were performed according to the protocols and guidelines of the institutional animal care and use committee. Mice were sacrificed at 7 days and 1, 2, 3, and 4 months after bleomycin or saline treatment. For every variable, six control and six experimental mice were used.
2013-03-11 | E-GEOD-42301 | biostudies-arrayexpress
Project description:A well-characterized mouse model of SSc involves daily subcutaneous injections of the antitumor antibiotic bleomycin (BLM), which leads to localized dermal fibrosis as well as pulmonary fibrosis. We have termed this the “Systemic Bleomycin Model” to distinguish it from the already-established Intratracheal (IT) model. We utilize this model, which mimics several key features of human SSc, to examine the pathological mechanisms underlying the development and progression of fibrosis in SSc.
2019-06-18 | GSE132869 | GEO
Project description:We perfomed a microRNA microarray on to assess differentially expressed miRNAs in bleomycin-induced lung fibrosis in mice. To induce pulmonary fibrosis, belomycine (Sigma-Aldrich, St Louis, MO) was dissolved and administred intratracheally at a dose of 1.5U/kg body weight. Control animals received saline only. 21 days post bleomycin treatment, mice were sacrificed and lung tissue were collected for RNA extraction and microRNA microarray.
2020-08-07 | GSE155823 | GEO