Initial Gene Epxression Responses to Bleomycin Treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE90879 | GEO | 2016/12/06
SECONDARY ACCESSION(S): PRJNA356269
REPOSITORIES: GEO
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Project description:To understand gene expression responses in confluent human fibroblast in microgravity conditions to bleomycin treatment.
2017-01-20 | GSE93860 | GEO
Project description:This experiment sought to characterize the epithelial-specific transcriptional response in the bleomycin model of lung fibrosis, and the contribution of IRE1a and the TGFb-activating integrin avb6 to this response. "Ribotag" mice were crossed to ShhCre mice, both on the C57BL/6 background to generate experimental cohorts. Mice used for the experiment conditionally expressed HA-tagged ribosomal protein Rpl22 in the epithelium. Mice were exposed to intranasal bleomycin (3 U/kg) on day 1 and subsequently treated with the IRE1a kinase inhibitor KIRA8 (50 mg/kg daily), or the anti-integrin beta6 antibody 3G9 (10 mg/kg on day 1 and day 4). Treatment controls were either drug vehicle (3% ethanol, 7% Tween80, and 90% saline) or the inert antibody Axum8 in saline). Lungs were harvested on day 7 after bleomycin exposure, flash-frozen, and later homogenized under native conditions with cycloheximide. An aliquot of the “input” homogenate was removed and total RNA purified by Qiagen RNeasy Mini and is representative of the whole-lung transcriptome/translatome. The remaining homogenate was subjected to immunoprecipitation of HA-tagged polysomes, followed by RNA purification by Qiagen RNeasy Micro, and is representative of the lung epithelial transcriptome/translatome.
2022-02-14 | GSE190821 | GEO
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: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:Gene expression analysis of C57BL/6 mice challenged by intratracheal bleomycin instillation: mRNA expression profiles were established from lungs following a 14-days PBS or bleomycin administration. One color -experiment with 1 strain of mice (C57BL/6) following a 14-days PBS or bleomycin administration (n=5), corresponding to a total of 10 samples.
2013-02-01 | E-GEOD-34814 | biostudies-arrayexpress
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:Comparison of C57BL/6 (sensitive) and BALB/c (resistant) mice challenged by intratracheal bleomycin instillation: miRNA expression profiles were established from lungs derived from the two strains, following a 7- or 14-days PBS or bleomycin administration. One color -experiment with 2 strains of mice (C57BL/6 and BALB/c) following a 7- or 14-days PBS or bleomycin administration (n=3), corresponding to a total of 24 samples.
2013-02-01 | E-GEOD-34812 | biostudies-arrayexpress
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.
2013-03-11 | GSE42301 | GEO
Project description:Hep3B cells were treated with the chemotherapeutic drug bleomycin. RNA was isolated after 18 h, 24 h and 36 h. The status of the gene expression was examined in response to treatment with bleomycin,
2009-09-01 | E-MEXP-1213 | 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. 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