Emphysema Lung Tissue Gene Expression Profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE1122 | GEO | 2004/06/01
SECONDARY ACCESSION(S): PRJNA87235
REPOSITORIES: GEO
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Project description:Gene expression profiling of lung tissue from undiseased (NML), 'usual' emphysema (EML), and Alpha-1 Antitrypsin Deficiency-related emphysema (ADL).
2007-07-19 | E-GEOD-1122 | biostudies-arrayexpress
Project description:QUANTitative Chest Computed Tomography UnMasking Emphysema Progression in Alpha-1 Antitrypsin Deficiency - RLDC 5701
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Project description:Patients with chronic obstructive pulmonary disease (COPD) having higher blood eosinophil levels exhibit worse lung function and more severe emphysema, implying the potential role of eosinophils in emphysema development. However, the specific mechanism underlying eosinophil-mediated emphysema development is not fully elucidated. In this study, single-cell RNA sequencing was used to identify eosinophil subgroups in mouse models of asthma and emphysema and analyze their functions. Analysis of the accumulated eosinophils revealed differential transcriptomes between the mouse lungs of elastase-induced emphysema and ovalbumin-induced asthma., Eosinophil depletion alleviated elastase-induced emphysema. Notably, eosinophil-derived cathepsin L (CTSL) degraded the extracellular matrix (ECM), causing emphysema in the pulmonary tissue. Eosinophils were positively correlated with serum CTSL levels, which were increased in patients with emphysema than in those without emphysema. Collectively, these results suggest that CTSL expression in eosinophils plays an important role in ECM degradation and remodeling and is related to emphysema in patients with COPD. Therefore, eosinophil-derived CTSL may serve as a potential therapeutic target for patients with emphysema.
2023-10-17 | GSE237749 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a heterogenous disorder marked by small airway inflammation and distal airspace enlargement (emphysema) leading to progressive airflow obstruction and eventual respiratory failure. Current therapies are limited in their ability to halt the pathogenesis of COPD merely relieving symptoms of dyspnea and airflow limitation. Microvasculature dysfunction, an understudied area of investigation, is associated with the severity of COPD. However, it is not known if abnormal lung endothelium drives COPD pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of specialized pulmonary endothelial cells to lung pathogenesis in an elastase-induced murine model of COPD. Airspace disease was marked by aberrant endothelial cell loss and dysfunction, which was rescued by intravenous delivery of healthy lung endothelial cells. Airspace injury triggered regulation of a distinct module of maladaptive endothelial transcripts comprising lost endothelial cell function. Endothelial leucine-rich alpha-2-glycoprotein-1 (LRG1) was identified as a key driver of the emphysematous pathology and selective deletion of Lrg1 from endothelial cells rescued elastase-induced defects of pulmonary parenchymal destruction. Hence, targeting lung endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent novel therapeutic strategies of immense potential for the treatment of emphysema.
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Project description:Exploratory design using pooled samples of 3 patients with emphysema and 3 patients without COPD Aim: 1.Search for expressed genes to select for a custom designed array (200 genes, n=50). 2. Find highly differentially expressed genes as targets for qPCR 3. Search for regulated senescent associated genes Keywords: disease comparison
2006-03-02 | GSE3510 | GEO
Project description:Comparison of severely emphysematous tissue removed at lung volume reduction surgery to that of normal or mildly emphysematous lung tissue resected from smokers with nodules suspicious for lung cancer. Data obtained from the 18 patients with severe emphysema and 12 patients with mild/no emphysema. Research may provide insights into the pathogenetic mechanisms involved in chronic obstructive pulmonary disease (COPD).
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Project description:To define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients.
2012-06-01 | GSE33336 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients. Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples. Class comparison identified 98 differentially expressed genes (p<0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p<0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity. Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.
2009-09-21 | GSE17770 | GEO
Project description:Chronic Obstructive Pulmonary Disease, which is comprised of chronic bronchitis and emphysema, is a leading cause of morbidity and mortality. Because tissue destruction is the prominent characteristic of emphysema, extracellular proteinases, particularly those with elastolytic ability, are often considered to be key drivers in this disease. Several human and mouse studies have implicated roles for matrix metalloproteinases (MMPs), particularly macrophage-derived proteinases, in COPD pathogenesis. MMP28 is expressed by the pulmonary epithelium and macrophage, and we have found that it regulates macrophage recruitment and polarization. We hypothesized that MMP28 would have contributory roles in emphysema via alteration of macrophage numbers and activation. Because of the established association of emphysema pathogenesis to macrophage influx, we evaluated the inflammatory changes and lung histology of Mmp28-/- mice exposed to 3 and 6 months of cigarette smoke. At earlier time-points, we found altered macrophage polarization in the smoke-exposed Mmp28-/- lung consistent with other published findings that MMP28 regulates macrophage activation. At both 3 and 6 months, Mmp28-/- mice had blunted inflammatory responses more closely resembling non-smoked mice, with a reduction in neutrophil recruitment and CXCL1 chemokine expression. By 6 months, Mmp28-/- mice were protected from emphysema. These results highlight a previously unrecognized role for MMP28 in promoting chronic lung inflammation and tissue remodeling induced by cigarette smoke and highlight another potential target to modulate COPD.
2017-02-18 | GSE93898 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disorder primarily induced by cigarette smoking, and characterized by persistent airflow limitation. The mouse represents an important model for studying COPD pathologies such as lung emphysema. In this respect, a number of mechanistic studies have been performed, however the approaches were mostly focused on single gene analysis or characterization of cellular, inflammatory or histopathological changes without attempting a more comprehensive interpretation. In the present study we aimed at applying systems biology approach to identify genome-wide molecular mechanisms indicative of cigarette smoke (CS)-induced lung emphysema. The lung transcriptomes of five mouse models (C57BL/6, ApoE-/-, A/J, CD1, and Nrf2-/-), that are known to be susceptible to CS-induced emphysema development, were analyzed following prolonged (5-6 months) CS exposure. The investigation resulted in the confirmation of many existing mechanistic explanations underlying smoke-induced lung emphysema, including increased transcriptional activity of NF-?B, and increased levels of TNF-a, IFN-g, and IL-1b. More importantly, we predicted mechanisms without currently well-documented roles, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1 and N-cor, and increased IL-17 cytokine expression, and reduced protein expression of ITGB6 and CFTR. We also corroborated, by using targeted proteomic approaches, several predictions such as reduced expression of ITGB6 and increased expression of BRCA1, C/EBPs, PU.1, TNF-a, IL-1b or CSF2. We believe this study will provide more insights into better understanding of CS-induced molecular processes underlying emphysema development in mice that may eventually be relevant in humans.
2014-11-28 | E-MTAB-2756 | biostudies-arrayexpress