Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA209046 | ENA |
REPOSITORIES: ENA
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Project description:Objective: Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results: We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion: Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively.
2013-06-21 | E-GEOD-48149 | biostudies-arrayexpress
Project description:Objective: Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results: We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion: Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease.
2013-06-21 | GSE48149 | GEO
Project description:Pulmonary hypertension (PH) is a common complication of systemic sclerosis (SSc) and a leading cause of mortality among patients with this disease. PH can also occur as an idiopathic condition (idiopathic pulmonary arterial hypertension, iPAH). We sought to investigate the transcriptomic alterations in PH vascular populations to understand cellular mechanisms underlying pathobiology of systemic sclerosis associated and idiopathic pulmonary hypertension.
2024-06-07 | GSE244781 | GEO
Project description:The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated PAH patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and PH (SSC-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Gene expression is compared at a global level using total RNA from BPMC for pateints and controls using the Illumina microarray platform.
2012-04-29 | E-GEOD-33463 | biostudies-arrayexpress
Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of mesenchymal cells and formation of scar tissue. Th2 T cell-derived cytokines including IL-4 and IL-13 have been shown to contribute to inflammation and fibrotic remodeling in multiple tissues. Interleukin-31 (IL-31) is a newly identified cytokine that is predominantly produced by CD4 Th2 T cells, but its signaling receptor IL-31RA is primarily expressed by non-hematopoietic cells. However, the potential role of the IL-31-IL31RA axis in pulmonary inflammation and fibrosis has remained largely unknown. To determine the role of IL-31 signaling in pulmonary fibrosis, wildtype, and IL-31RA knockout mice were treated with bleomycin and measured changes in total lung transcripts using RNA-seq. The total lung transcriptome analysis showed a significant reduction in fibrosis-associated gene transcripts including extracellular matrix and epithelial cell-associated gene networks.
2020-12-23 | GSE163740 | GEO
Project description:The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated PAH patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and PH (SSC-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals.
2012-04-30 | GSE33463 | GEO
Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of stromal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent animals models generated in our lab demonstrate clinical phenotypes seen in human fibrotic disease. The mouse model of transforming growth factor-? (TGF?)-induced fibrosis include conditionally expressing TGF? in the lung epithelium under control of the CCSP promoter driving rtTA expression (CCSP/TGF?). This allow the TGF? is only expressed in airway and alveolar epithelial cells and only when mice fed doxycycline (Dox). Similar to PF in humans, TGF? mice on Dox developed a progressive and extensive adventitial, interstitial and pleural fibrosis with a decline in lung mechanics. Thus, the TGF? transgenic mouse is a powerful model to determine lung cell-specific molecular signatures involved in pulmonary fibrosis. In this study, we sought to determine changes in the transcriptome during TGF?-induced pulmonary fibrosis. Our results showed that several pro-fibrotic genes increased in the lungs of TGF? mice. This study demonstrates that WT1 network gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a critical regulator fibrotic lung disease. mRNA profiles of CCSP/- and CCSP/TGFalpha mice treated with Dox
2015-03-07 | E-GEOD-66634 | biostudies-arrayexpress
Project description:Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper-lobe emphysema combined with lower-lobe fibrosis and a high prevalence of pulmonary hypertension. The aim of this study was to measure and analyze gene expression profiles in the lungs of CPFE patients. The results showed that the expression profiles of the fibrotic and emphysematous lesions were remarkably different in terms of function. Genes related to immune system, structural constituents of cytoskeleton, and cellular adhesion were overexpressed in fibrotic lesions, while genes associated with cellular fraction, cell membrane structures, vascular growth and biology, second-messenger-mediated signaling, and lung development (all processes that contribute to the destruction and repair of cells, vessels, and lung) were overexpressed in emphysematous lesions. The differences in gene expression were detected in fibrotic and emphysematous lesions in CPFE patients. We propose that the development of coexisted fibrotic and emphysematous lesions in CPFE is implemented by these different patterns of gene expressions. Lung tissue specimens from fibrous lesions and emphysematous lesions of 3 patients with combined pulmonary fibrosis and emphysema (CPFE) were obtained for RNA extraction and hybridization on Affymetrix microarrays. We hypothesized that coexisted fibrosis and emphysema in CPFE are programmed by differential gene expressions in the corresponding lesions in the lungs of smokers susceptible to CPFE. Given the importance of genetic susceptibility in understanding the etiology and pathogenesis of CPFE, we examined tissues from patients with CPFE to systemically identify genes significantly expressed in lung tissues with fibrotic lesions as well as genes significantly expressed in tissues with emphysematous lesions.
2012-06-26 | E-GEOD-38934 | biostudies-arrayexpress
Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of mesenchymal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and mesenchymal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Our new findings have identified the aberrant activation of Sox9 in lung resident fibroblasts and myofibroblasts in IPF lung biopsies and the mouse model of transforming growth factor-α (TGFα) and bleomycin-induced pulmonary fibrosis. In this study, we sought to determine Sox9-driven gene networks in lung resident fibroblast during pulmonary fibrosis. Our results showed that Sox9 regulates the transcriptional changes that are required for the fibroblast activation including migration, myofibroblast transformation, survival and extracellular matrix deposition during pulmonary fibrosis. In summary, this new study demonstrates that Sox9 is a critical regulator of fibroblast activation in IPF and hence serve as a target for therapeutic intervention.
2021-12-31 | GSE171532 | GEO
Project description:Pulmonary fibrosis develops as a consequence of environmentally induced lung injury and/or an inherent disease susceptibility causing fibroblast activation, proliferation and extracellular matrix deposition. The study was undertaken to characterise global gene expression in pulmonary fibroblasts to better understand the mechanisms underlying the fibrotic fibroblast phenotype. Gene expression was evaluated in lung fibroblasts derived from ten controls (normal periphery of resected tumor), open lung biopsies from eight patients with interstitial lung disease associated with systemic sclerosis (fibrotic non specific interstitial pneumonia pattern on biopsy), and from three patients with usual interstitial pneumonia. Lung fibroblasts were grown to confluence in DMEM with 10% fetal calf serum. At confluence, lung fibroblasts were serum-deprived for 44 hours in the presence of fibroblast growth medium with the addition of 0.1% bovine serum albumin (Sigma).
2013-08-05 | E-GEOD-40839 | biostudies-arrayexpress