Quantitative_Proteomic_Profiling_of_Extracellular_Matrix_and_collagen_post-translational_modifications_induced_by_transforming_ growth_factor_b1_on_the_lung_fibroblast
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Roberto Vanacore
PROVIDER: MSV000082958 | MassIVE |
REPOSITORIES: MassIVE
Similar Datasets
Project description:Analysis of gene expression of lung fibroblasts seeded onto decellularized extracellular matrix (ECM). Experiment had 2x2 design where fibroblasts from idiopathic pulmonary fibrosis (IPF) or control patients were seeded onto decelluarized lung tissue from IPF or control patients allowing for determination of gene expression differences that were driven by IPF ECM and which differences were driven by the IPF fibroblast.
2014-03-04 | GSE45686 | GEO
Project description:Analysis of gene expression of lung fibroblasts seeded onto decellularized extracellular matrix (ECM). Experiment had 2x2 design where fibroblasts from idiopathic pulmonary fibrosis (IPF) or control patients were seeded onto decelluarized lung tissue from IPF or control patients allowing for determination of gene expression differences that were driven by IPF ECM and which differences were driven by the IPF fibroblast. Lung fibroblasts from 5 patients with idiopathic pulmonary fibrosis and 5 control patients were cultured on decellularized ECM from IPF or control lung. Total RNA and polyribosome RNA were isolated after the cells were cultured on the decellularized ECM for 18 hours. When possible, a control cell line and a diseased cell line were cultured (and processed) simultaneously to minimize the effect of experimental variance induced by running the experiment at different times.Samples with the same batch number (provied in the sample 'characteristics' field) were cultured and processed at the same time.
2014-03-04 | E-GEOD-45686 | biostudies-arrayexpress
Project description:We performed a PCR array of 84 ECM-related genes using RNA obtained from dermal fibroblasts stimulated with or without EBI3. 18 of the 84 genes were upregulated and 22 genes were downregulated in EBI3-treated fibroblasts in comparison with untreated cells. In the present study, we examined the involvement of the IL-12 family cytokines in the expression of the extracellular matrix.
2015-05-08 | E-GEOD-68649 | biostudies-arrayexpress
Project description:Myofibroblasts are key effector cells in the extracellular matrix remodeling of systemic sclerosis-associated interstitial lung disease (SSc-ILD), however the diversity of fibroblast populations present in the healthy and SSc-ILD lung is unknown, and has prevented the specific study of the myofibroblast transcriptome. We sought to identify and define the transcriptomes of myofibroblasts and other mesenchymal cell populations in human healthy and SSc-ILD lungs to understand how alterations in fibroblast phenotypes lead to SSc-ILD fibrosis.
2019-08-14 | GSE128169 | GEO
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:Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible fibrotic disease of the distal lung alveoli that culminates in respiratory failure and reduced lifespan. Unlike normal lung repair in response to injury, IPF is associated with the accumulation and persistence of fibroblasts and myofibroblasts and continued production of collagen and other extracellular matrix (ECM) components. Prior in vitro studies have led to the hypothesis that the development of resistance to Fas-induced apoptosis by lung fibroblasts and myofibroblasts contibributes to their accumulation in the distal lung tissues of IPF patients. Here, we test this hypothesis in vivo in the resolving model of bleomycin-induced pulmonary fibrosis in mice. Using genetic loss-of-function approaches to inhibit Fas signaling in fibroblasts, novel flow cytometry strategies to quantify lung fibroblast subsets and transcriptional profiling of lung fibroblasts by bulk and single cell RNA-sequencing, we show that Fas is necessary for lung fibroblast apoptosis during homeostatic resolution of bleomycin-induced pulmonary fibrosis in vivo. Furthermore, we show that loss of Fas signaling leads to the persistence and continued pro-fibrotic functions of lung fibroblasts. Our studies provide novel insights into the mechanisms that contribute to fibroblast survival, persistence and continued ECM deposition in the context of IPF and how failure to undergo Fas-induced apoptosis prevents fibrosis resolution.
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Project description:Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by progressive destruction of normal alveolar gas-exchange surfaces and accumulation of extracellular matrix (ECM). In order to comprehensively define the cell types, mechanisms and mediators driving ECM deposition and fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing (scRNA-seq) of single-cell suspensions generated from non-fibrotic control and PF lungs. Analysis of over 114,000 cells from 20 PF and 10 control lungs identified 31 distinct cell types. We identified multiple distinct lineages directly contribute to ECM expansion, including a novel HAS1hi fibroblast subtype and a previously undescribed KRT5-/KRT17+, collagen and ECM-producing epithelial cell population that was highly enriched in PF lungs. Together these data provide high-resolution insights into the basic mechanisms of pulmonary fibrosis, and indicate a direct profibrotic role of the lung epithelium in PF pathogenesis.
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Project description:<p>The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.</p><p><br></p><p>Linked studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS1977' rel='noopener noreferrer' target='_blank'>MTBLS1977</a></p>
2020-10-07 | MTBLS1969 | MetaboLights
Project description:<p>The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.</p><p><br></p><p>Linked studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS1969' rel='noopener noreferrer' target='_blank'>MTBLS1969</a></p>
2020-10-07 | MTBLS1977 | MetaboLights
Project description:Fibroblasts are the main producers of extracellular matrix (ECM) responsible for ECM maintenance and repair, a process often disrupted in chronic lung diseases. The accompanying mechanical changes adversely affect resident cells and overall lung function. Numerous models have been used to elucidate fibroblast behavior which are now evolving towards complex 3D models incorporating ECM, aiming to replicate the cells’ native environment. Little is known about the cellular changes that occur when moving from 2D to 3D cell culture. This study compared gene expression profiles of primary human lung fibroblasts from 7 subjects with normal lung function, cultured for 24 hours on 2D collagen I-coated tissue culture plastic and in 3D collagen I hydrogels, which are commonly used to mimic ECM in various models, from contraction assays to organ-on-a-chip models. Comparing 3D to 2D cell culture, 6,771 differentially expressed genes (2,896 up, 3,875 down) were found; enriched gene sets within the downregulated genes, identified through Gene Set Enrichment Analysis and Ingenuity pathway analysis, were involved in the initiation of DNA replication which implied downregulation of fibroblast proliferation in 3D. Observation of cells for 72 hours in 2D and 3D environments confirmed the reduced progression through the cell cycle in 3D. A focused analysis examining the Hippo pathway and ECM-associated genes, showed differential patterns of gene expression in the 3D versus 2D culture. Altogether, the transcriptional response of fibroblasts cultured in 3D indicated inhibition of proliferation, and alterations in Hippo and ECM pathways indicating a complete switch from proliferation to ECM remodeling.
2023-11-13 | GSE247220 | GEO