Expression data in lung tissue from moderate COPD patients, healthy smokers and nonsmokers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37768 | GEO | 2016/08/25
SECONDARY ACCESSION(S): PRJNA163249
REPOSITORIES: GEO
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Project description:Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory lung disease. The abnormal inflammatory response of the lung, mainly to cigarette smoke, causes multiple cellular and structural changes affecting all of its compartments, which leads to disease progression. The molecular mechanisms underlying these pathological changes are still not fully understood The aim of this study was to identify genes and molecular pathways potentially involved in the pathogenesis of COPD Peripheral lung tissue samples from moderate COPD patients, smokers and nonsmokers were obtained. All patients were undergoing lung resection for localized carcinomas. RNA was extracted and processed for further hybridization on Affymetrix microarrays
2016-08-25 | E-GEOD-37768 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation，obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, e.g. cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers.
2019-06-21 | GSE133096 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2015-08-28 | PXD001977 | Pride
Project description:Epigenetics changes have been shown to be affected by cigarette smoking. It is possible that cigarette smoke (CS)-mediated DNA methylation would affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from lung tissues of patients including 8 lifelong non-smokers, 8 current smokers, and 8 patients with COPD, and subsequently analyzed the samples using the Illumina’s Infinium HumanMethylation450 BeadChip.
2017-06-12 | GSE92511 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2015-08-28 | E-MTAB-3604 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2016-10-21 | MSV000080275 | MassIVE
Project description:Rationale: Chronic Obstructive Pulmonary Disease (COPD) is associated with a complex pulmonary and systemic immune response. Objective: To characterize and relate the lung tissue and circulating blood network immune response in COPD. Methods: Lung tissue and circulating blood samples were simultaneously obtained from COPD patients (current smokers n=28 and former smokers n=16) and controls (current smokers n=9 and non-smokers n=12) undergoing thoracic surgery. We used flow cytometry to assess the immune cell composition, Affymetrix arrays to determine whole lung mRNA expression, and Weighted Gene Co-expression Network Analysis (WGCNA) to characterize and compare the pulmonary and systemic immune responses in patients and controls. Results: In lung tissue of current smokers with COPD (vs. non-smokers and former smokers with COPD) we observed a significant increase in the proportion of intermediated phenotype macrophages (Mphage) expressing both M1 and M2 markers, whereas that of M1 Mphage (pro-inflammatory) and CD4+ and CD8+ T-lymphocytes were decreased. These changes were not mirrored in circulating blood but WGCNA identified three modules of co-expressed genes that related, respectively to: (1) the total proportion of lung Mphage (extracellular matrix and angiogenesis genes) ; (2) active smoking (T cell and apoptosis related genes); and, (3) severity of airflow limitation (cilium organization genes). Conclusions: In mild/moderate COPD, the main pulmonary immune cell alterations relate to current smoking, involve changes in the proportion of Mphage and T cells and are associated with changes in whole lung tissue transcriptome. These cellular pulmonary changes are not mirrored in the systemic circulation.
2018-07-01 | GSE103174 | GEO
Project description:Background: When exposed to specific stimuli, macrophages exhibit distinct activation programs, M1 and M2 polarization, that define macrophage function as inflammatory/immune effectors or anti-inflammatory/tissue remodeling cells, respectively. Due to their position on the lung epithelial surface, alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for the development of chronic obstructive pulmonary disease (COPD). Based on the current paradigm that, in response to smoking, AM contribute to both inflammatory and tissue remodeling processes in the lung relevant to the pathogenesis of COPD, we hypothesized that chronic exposure to cigarette smoking activates both the M1 and M2 polarization programs in AM. Methods and Findings: To assess this hypothesis, global transcriptional profiling with TaqMan confirmation and flow cytometry analysis was carried out on AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers and 12 smokers with COPD to assess the expression of 41 M1 genes and 32 M2 genes in each group. Contrary to our expectations, while there was up-regulation of some genes typical for M2-related phenotypes, AM of healthy smokers exhibited substantial suppression of M1-related inflammatory/immune genes. These M1- and M2-related changes progressed with the development of smoking-induced lung disease, with AM of smokers with COPD exhibiting further down-regulation of M1-related genes accompanied with further up-regulation of some M2-related genes. Conclusion: The data demonstrates that the modifications of the AM transcriptome associated with smoking result in a unique phenotype characterized by reprogramming of AM towards M1-deactivated partially M2-polarized macrophages and suggests that, while AM likely contribute to smoking-induced tissue remodeling, the role of AM in the early pathogenesis of smoking-induced COPD in humans is not inflammatory. This concept is a departure from the conventional concept that AM-mediated inflammation participates in the early derangements of the lung induced by smoking, and suggests a novel paradigm for conceptualizing COPD and developing new approaches to prevent the development of smoking-induced lung disease. Comparison of gene expression in alveolar macrophages of normal non-smokers and normal smokers and smokers with COPD
2009-08-09 | E-GEOD-13896 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients. Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.
2014-12-04 | E-GEOD-52509 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by persistent and amplified inflammation to cigarette smoke in vulnerable subjects. The genetic risk of persistent inflammation is poorly understood. A mouse model targeting hedgehog interacting protein (HHIP)(Hhip+--), a genetic risk factor for COPD, displays progressive, persistent inflammation resembling human cases, providing a valuable model to study the contribution of the genetic risk factor HHIP to inflammation in COPD. By single cell RNA sequencing of Hhip+-- lungs at different disease stages, we identified induction of IFN-gamma in activated CD8+T cells possibly driving the inflammatory phenotype in Hhip+-- lungs. Hhip expression was restricted to lung fibroblasts, which interaction with CD8+T cells were mediated by increased levels of IL-18 from Hhip+-- fibroblasts. Our finding provides insight into how a common genetic variation contributes to the amplified lymphocytic inflammation in COPD.
2021-08-01 | GSE149843 | GEO