Comparison of transcriptional changes in IPF mouse models (Bleomycin and Ad-TGFb)
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PROVIDER: PRJNA739151 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications.We investigated the anti-fibrotic efficacy of saracatinib in two in vivo modeles (bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis).
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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: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.
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Project description:Idiopathic pulmonary fibrosis (IPF) is a progressing chronic and fibrotic lung response with poor prognosis. To study the underlying molecular mechanisms of IPF, the rat bleomycin model is commonly used. Intratracheal application of bleomycin is known to induce inflammatory and fibrotic processes in the lung, e.g. infiltratin of inflammatory cells and collagen deposition. Recently, the PDE4B inhibitor BI 1015550 has been reported to prevent a decrease in lung function in patients with IPF. Here we examined the effect of PDE4 inhibitor BI 1015550 in the rat bleomycin model on transcriptional level by RNASeq.
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Project description:Idiopathic pulmonary fibrosis (IPF) is a complex disease involving various cell types. Macrophages are essential in maintenance of physiological homeostasis, wound repair and fibrosis in the lung. Macrophages play a crucial role in repair and remodeling by altering their phenotype and secretory pattern in response to injury. The secretome of induced pluripotent stem cells (iPSC-cm) attenuates injury and fibrosis in bleomycin injured rat lungs. In the current study, we evaluate the effect of iPSC-cm on interstitial macrophage gene expression and phenotype in bleomycin injured rat lungs in vivo. Â iPSC-cm was intratracheally instilled 7 days after bleomycin induced lung injury and assessed 7 days later and single cell isolation was performed. Macrophages were FACS sorted and microarray analysis was performed. We characterized changes in the rat lung interstitial macrophages using transcriptional profiling.
2017-03-20 | E-MTAB-5619 | biostudies-arrayexpress
Project description:mRNA level comparison of control and IPF
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Project description:In USA, approximately 50,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) annually; and almost 40,000 of them die. IPF is a condition in which an injury to the lung leads to accumulation of scar tissue. This fibrotic tissue impairs the lungs’ ability to absorb necessary amount of oxygen. The exact etiology of IPF is unknown, but recent evidence suggests that the distal small airways (those having a diameter of less than 2mm) play a role in the early pathogenesis of IPF. Pathologic features of IPF include increased collagen deposition, the collapse of distal small airways, and the buildup of fibroblast/myofibroblast cells. Many of these features are also observed in the lungs of patients following COVID-19 infection. IPF patients who suffer from infection by COVID-19 have poor clinical outcomes and may require a lung transplant due to a significant increase in fibrotic tissue following the illness. This study aimed to investigate possible mechanisms that contribute to worsening lung fibrosis in IPF patients after being diagnosed with COVID-19. Small airway cell cultures derived from IPF and post-COVID-19 IPF patient transplant tissues along with normal lungs were submitted for RNA-sequencing and subsequent differential gene expression analysis. It has been observed that TGFB pathway is activated upon lung injury or illness, signalling profibrotic cascade. Thus, while culturing small airways ,fraction of cells were treated with TGFB.
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