Transcriptional profile of mouse lung during the fibrotic phase of the response to bleomycin
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE16846 | GEO | 2009/07/07
SECONDARY ACCESSION(S): PRJNA117619
REPOSITORIES: GEO
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Project description:Wildtype mice were given saline or bleomycin by oropharyngeal instillation. After 14 days, during the fibrotic phase of the response, lungs were dissected and total RNA was extracted and used for gene expression profiling. The aim was to identify those genes regulated during the development of fibrosis in this animal model of bleomycin-induced lung fibrosis. Wildtype male C57Bl/6J mice (8-10 weeks old) were used in the study, with three mice per group. Bleomycin (1mg/kg body weight in 50μl of saline) or saline was administered by oropharyngeal installation as described previously by Lakatos et al, Exp Cell Res, 2006, under light halothane-induced anaesthesia. After 14 days, lungs were removed, blotted dry and the trachea and major airways were excised before the separated lobes were snap frozen in liquid nitrogen. Lungs were then pulverized under liquid nitrogen, and the resulting lung powder was used for total RNA extraction using Trizol. Following DNase-treatment, clean-up, cDNA synthesis and cRNA synthesis, samples were hybridized to Affymetrix MOE430A genechips using standard protocols. The data were analyzed using RMA with quantiles normalization.
2009-07-07 | E-GEOD-16846 | 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: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:Fibroblast activation is transient in successful wound repair, but persistent in fibrotic pathologies. Understanding fibroblast deactivation during successful wound healing may provide new approaches to therapeutically reverse fibrogenic cell activation. To characterize the gene programs that accompany fibroblast activation and reversal during lung fibrosis resolution, we used RNA-seq analysis of flow-sorted Col1α1-GFP positive and CD45, CD31, and CD326 negative cells isolated from the lungs of young mice exposed to bleomycin and pneumonectomy. We compared fibroblasts isolated from controls to those isolated at days 14 and 30 after bleomycin exposure, as well as at 14 days after pneumonectomy, representing the peak of extracellular matrix deposition, early stage of fibrosis resolution, and non-fibrotic lung repair respectively.
2020-11-13 | GSE161322 | GEO
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: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: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. Old mice showed delayed and incomplete lung function recovery 8 weeks after Bleomycin instillation. This shift in structural and functional repair in old Bleomycin-treated mice was reflected in a temporal shift in gene and protein expression. We reveal gene signatures and signaling pathways which underpin the lung repair process.
2023-10-16 | GSE218997 | GEO
Project description:To study the possible fibrotic role of FIZZ2, bleomycin was used to induce pulmonary fibrosis in wild type and FIZZZ2 knockout mice, lungs were then harvested and processed for RNA isolation. We used microarrays to detail the global gene expression regulated by FIZZ2 during fibrotic process. Bleomycin/saline treated wild type or FIZZ2 knockout lungs at day 21 post injection were harvested for RNA isolation and hybridization on Affymetrix microarrays
2010-11-29 | E-GEOD-25640 | biostudies-arrayexpress
Project description:Collagen deposition is a key process during idiopathic pulmonary fibrosis (IPF); however, little is known about the dynamics of collagen formation during disease development. Tissue samples of early stages of human disease are not readily available and it is difficult to identify changes in collagen content, since standard collagen analysis does not distinguish between 'old' and 'new' collagen. Therefore, the current study aimed to (i) investigate the dynamics of new collagen formation in mice using bleomycin-induced lung fibrosis in which newly synthesized collagen was labelled with deuterated water and (ii) use this information to identify genes and processes correlated to new collagen formation from gene expression analysis. Lung fibrosis was induced in female C57BL/6 mice by bleomycin instillation and sacrificed. Animals were sacrificed at 1 to 5 weeks after fibrosis induction. Collagen synthesized during the week before sacrifice was labelled with deuterium by providing mice with deuterated drinking water. After sacrifice, lung tissue was collected for microarray analysis, determination of new collagen formation, and histology. Deuterated water labelling showed a strong increase in new collagen formation already during the first week after fibrosis induction and a complete return to baseline at five weeks. Correlation of new collagen formation data with gene expression data revealed fibrosis specific processes, of which proliferation was an unexpected one. This was confirmed by measuring cell proliferation and collagen synthesis simultaneously using deuterated water incorporation. Furthermore, new collagen formation strongly correlated with gene expression of e.g. elastin, tenascin C, MMP-14, lysyl oxidase, and type V collagen. These data demonstrate, using a novel combination of technologies, that proliferation and extracellular matrix production are correlated to the core process of fibrosis, i.e. the formation of new collagen. In addition, it identified genes directly correlated to fibrosis, thus providing more insight into the aetiology of IPF. Total RNA was obtained from mouse lungs at timepoint 0 as a control (n = 7) or timepoints 1 (n = 7), 2 (n = 6), 3 (n = 6), 4 (n = 6) or 5 (n = 6) weeks after bleomycin-instillation to induce lung fibrosis.
2013-05-26 | E-GEOD-37635 | biostudies-arrayexpress