Transcriptomic changes driving pulmonary fibrosis resolution in young and old Bleomycin-treated mice
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PROVIDER: PRJNA906540 | ENA |
REPOSITORIES: ENA
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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: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: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: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:Young and old mice were first injected with bleomycin. At day 0, day 4 and day 14, the lungs were harvested and digested, and Lin-Epcam+ cells were isolated with FACS, single-cell RNA-seq was performed with the FACS-sorted cells.
2022-05-24 | GSE157995 | GEO
Project description:Pulmonary fibrosis is a disease characterized by inflammatory cell infiltration, scar formation, deposition of extracellular matrix, alveolar epithelial cell injury and hyperplasia. To determine if alterations in microRNA expression contribute to these phenotypes, microRNA expression profiling of the lungs from bleomycin treated C57Bl/6J mice, relative to that of untreated controls, was undertaken. Mice were treated at 8 weeks old with 100 Units/kg of bleomycin delivered subcutaneously with osmotic minipumps. At 42 days post treatment mice were euthanized and lung microRNA isolated. We identified 11 microRNA's to be significantly differentially expressed (FDR threshold of 0.01) in the lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. These included bleomycin upregulated miR-34a, 335-5p, 207, 21, 301a, 146b, 199a-5p, and 449a and bleomycin downregulated miR-151-3p, 26a and 676. We have previously shown that 1558 genes are differentially expressed in the lungs of bleomycin treated mice. Of the 1412 targets of upregulated microRNAs, 142 were confirmed to be downregulated in the gene expression profile (GEP). Of the 583 targets of downregulated microRNAs, 53 were confirmed to be upregulated in the gene expression profile. Pathway analysis of the microRNA targets and GEP overlapping genes indicated that altered microRNA expression is associated with cellular development, cellular growth, cellular proliferation and changed tissue/cell morphology. Specific pathways include HGF signaling, Cholecystokinin/Gastrin-mediated signaling, Endothelin-1 signaling, RAR activation, Phospholipase C signaling and IGF1 signaling. We conclude that altered microRNA expression is a feature of pulmonary fibrosis which putatively influences components of the altered airway disease. Two condition study, C57Bl/6J mice treated with 100 Units/kg bleomycin and untreated controls. Biological replicated n =3 for each group. Left lung tissue.
2013-09-01 | E-GEOD-45789 | biostudies-arrayexpress
Project description:We conducted fibroblast-specific transcriptome analysis by next generation sequencing in order to investigate qualitative change and activation signatures of lung fibroblasts in bleomycin-induced pulmonary fibrosis. Lung fibroblasts were identified by using reporter mice of collagen-α2(I), in which collagen I-producing fibroblasts were labeled with EGFP. Lungs were dissociated with protease sollution, and single cell suspension were stained with lineage markers (Ter119, CD45, CD31, EpCAM). Lineage- GFP+ cells were sorted out and mRNA was collected. Using serial analysis of gene expression (SAGE) method, we identified 2,973,937 SAGE tags (1,080,798 tags from saline-treated GFP+ fibroblasts and 1,893,139 tags from bleomycin-treated GFP+ fibroblasts). We found that genes related to extracellular matrix construction were highly up-regulated in fibroblasts from belomycin-treated lungs. Moreover, an analysis of mRNA profiles revealed biological functions such as proliferation, invasion, adhesion, and migration were promoted in fibroblasts from bleomycin-treated lung, which recapitulated the role of fibroblasts in the fibrogenesis. These fibroblast-specific gene expression profiles will be important notions in future fibrosis studies. mRNA profiles of Lung fibroblasts from 3 mice at day 14 after saline or bleomycin treatment.
2013-07-22 | E-GEOD-42564 | biostudies-arrayexpress
Project description:Pulmonary fibrosis is a disease characterized by inflammatory cell infiltration, scar formation, deposition of extracellular matrix, alveolar epithelial cell injury and hyperplasia. To determine if alterations in microRNA expression contribute to these phenotypes, microRNA expression profiling of the lungs from bleomycin treated C57Bl/6J mice, relative to that of untreated controls, was undertaken. Mice were treated at 8 weeks old with 100 Units/kg of bleomycin delivered subcutaneously with osmotic minipumps. At 42 days post treatment mice were euthanized and lung microRNA isolated. We identified 11 microRNA's to be significantly differentially expressed (FDR threshold of 0.01) in the lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. These included bleomycin upregulated miR-34a, 335-5p, 207, 21, 301a, 146b, 199a-5p, and 449a and bleomycin downregulated miR-151-3p, 26a and 676. We have previously shown that 1558 genes are differentially expressed in the lungs of bleomycin treated mice. Of the 1412 targets of upregulated microRNAs, 142 were confirmed to be downregulated in the gene expression profile (GEP). Of the 583 targets of downregulated microRNAs, 53 were confirmed to be upregulated in the gene expression profile. Pathway analysis of the microRNA targets and GEP overlapping genes indicated that altered microRNA expression is associated with cellular development, cellular growth, cellular proliferation and changed tissue/cell morphology. Specific pathways include HGF signaling, Cholecystokinin/Gastrin-mediated signaling, Endothelin-1 signaling, RAR activation, Phospholipase C signaling and IGF1 signaling. We conclude that altered microRNA expression is a feature of pulmonary fibrosis which putatively influences components of the altered airway disease.
2013-09-01 | GSE45789 | GEO
Project description:Single-cell RNA-sequencing of bleomycin-injured young and old mice
| PRJNA663600 | ENA
Project description:Genomic profiling of bleomycin- and saline-treated mice across 7 timepoints (1, 2, 7, 14, 21, 28, 35 days post treatment) was carried out in C57BL6/J mice to determine the phases of response to bleomycin treatment which correspond to onset of active pulmonary fibrosis. Temporal genomic characterization of lung homogenate from male C57BL6/J mice treated intratracheally with bleomycin or saline was carried out at 7 timepoints post treatment (1, 2, 7, 14, 21, 28, 35 days). Bleomycin (2U/kg) in 50 μl was intratracheally sprayed once into mice lightly anaesthetized with isoflurane (5% in 100% O2). Control animals received 50 μl of saline. Total RNA was isolated from the mouse lung tissue of bleomycin- and saline-treated mice across the 7 time points (n=8 per group) and homogenized in QIAzol reagent. Purified total RNA was amplified and labeled using NuGen Ovation kits (NuGEN Technologies, Inc., San Carlos, CA), and RNA from samples was hybridized to Affymetrix Mouse 430 2.0 arrays. One sample (saline treated, d14) was flagged as an outlier in principal component analysis and removed from subsequent analysis.
2013-04-10 | E-GEOD-40151 | biostudies-arrayexpress