Homo sapiens
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PROVIDER: PRJNA163249 | ENA |
REPOSITORIES: ENA
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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:Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Considering this, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, we found three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.
2021-08-13 | GSE180651 | GEO
Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies.
2014-02-03 | GSE43939 | GEO
Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.
2014-02-03 | E-GEOD-43939 | biostudies-arrayexpress
Project description:CXCL14, a recently described chemokine constitutively expressed in various epithelia, has multiple putative roles in inflammation and carcinogenesis. Based on the knowledge that cigarette smoking and the smoking-induced disorders, such as chronic obstructive pulmonary disease (COPD) and lung cancer, are associated with inflammation, we hypothesized that the airway epithelium, the primary site of smoking-induced pathologic changes in COPD and adenocarcinoma, responds to cigarette smoking with an altered CXCL14 gene expression as a part of disease-relevant molecular phenotype. Microarray analysis with subsequent TaqMan PCR validation revealed very low constitutive CXCL14 gene expression in the airway epithelium of healthy nonsmokers (n=53) which was strongly up-regulated in healthy smokers ( n=59; p<0.001) and further increased in COPD smokers (n=23; p<10-7 vs nonsmokers; p<0.005 vs healthy smokers). In smokers, CXCL14 expression inversely correlated with lung function parameters FEV1 and FEV1/FVC. Genome-wide analysis also showed that up-regulated correlation of CXCL14 expression with genes related to cell growth and proliferation, squamous differentiation and cancer. The analysis of 193 lung adenocarcinoma samples demonstrated a dramatic up-regulation of CXCL14 in a smoking-dependent manner. [need to include survival data once we get it]. Together, these data suggest that smoking-induced expression of CXCL14 in association with genome-wide reprogramming of processes related to tissue homeostasis, differentiation and tumorigenesis, represents a novel molecular link between cigarette smoking, COPD and lung cancer.
2024-06-05 | GSE21359 | GEO
Project description:Cystatin A (gene: CSTA), is up-regulated in non-small-cell lung cancer (NSCLC) and dysplastic vs normal human bronchial epithelium. In the context that chronic obstructive pulmonary disease (COPD), a small airway epithelium (SAE) disorder, is independently associated with NSCLC (especially squamous cell carcinoma, SCC), but only occurs in a subset of smokers, we hypothesized that genetic variation, smoking and COPD modulate CSTA gene expression levels in SAE, with further up-regulation in SCC. Gene expression was assessed by microarray in SAE of 178 individuals [healthy nonsmokers (n=60), healthy smokers (n=82), and COPD smokers (n=36)], with corresponding large airway epithelium (LAE) data in a subset (n=52). Blood DNA was genotyped by SNP microarray. Twelve SNPs upstream of the CSTA gene were all significantly associated with CSTA SAE gene expression (p<0.04 to 5 x 10-4). CSTA gene expression levels in SAE were higher in COPD smokers (28.4 ± 2.0) than healthy smokers (19.9 ± 1.4, p<10-3), who in turn had higher levels than nonsmokers (16.1 ± 1.1, p<0.04). CSTA LAE gene expression was also smoking-responsive (p<10-3). Using comparable publicly available NSCLC expression data, CSTA was up-regulated in SCC vs LAE (p<10-2) and down-regulated in adenocarcinoma vs SAE (p<10-7). All phenotypes were associated with significantly different proportional gene expression of CSTA to cathepsins. The data demonstrate that regulation of CSTA expression in human airway epithelium is influenced by genetic variability, smoking, and COPD, and is further up-regulated in SCC, all of which should be taken into account when considering the role of CSTA in NSCLC pathogenesis. CSTA gene expression was assessed in the small airway epithelium obtained by bronchoscopy from 178 individuals, including healthy nonsmokers (n= 60) and healthy smokers (n= 118) and the large airway epithelium from healthy nonsmokers (n=21) and healthy smokers(n=31). *** Processed data not provided for all gene expression records. *** Blood DNA from the majority of these individuals was genotyped and an association analysis of gene expression with genotypes of all 48 SNPs within 100 kb of CSTA was performed in PLINK, and tested for significance following 103 permutations within ancestral clusters. Supplementary file (linked below) reports genotypes of all 48 SNPs within 100 kb of the CSTA gene for the 112 genotyping Samples.
2012-06-19 | E-GEOD-22047 | biostudies-arrayexpress
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: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:The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. Based on the knowledge that smokers are more susceptible to pulmonary infection and the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters the expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th-12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most strikingly changed gene is TLR5, which down-regulated in healthy smokers (1.4-fold decrease, p<10-13) and in smokers with COPD (1.6-fold, p<10-14). TaqMan RT-PCR confirmed these observations. Bronchial biopsies immunofluorescence showed that TLR5 protein was expressed mainly on the apical side of the human airway epithelium and decreased in healthy smokers and smokers with COPD. In vitro studies showed that the level of TLR5 downstream genes, IL-6 and IL-8 were highly induced in TLR5 high-expressing cells compared to TLR5 low-expressing cells after flagellin exposure. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 likely contributes to smoking-related susceptibility to airway infection. The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense. Microarrays were used to survey the TLR family gene expression in small airway (10th-12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most strikingly changed gene is TLR5, which down-regulated in healthy smokers (1.4-fold decrease, p<10-13) and in smokers with COPD (1.6-fold, p<10-14). In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 likely contributes to smoking-related susceptibility to airway infection. *** Processed data not provided for all gene expression records. ***
2012-10-03 | E-GEOD-30063 | biostudies-arrayexpress
Project description:The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. Transcriptome analysis revealed a global down-regulation of physiological AJC gene expression in the SAE of healthy smokers (n=53) compared to healthy nonsmokers (n=59), an observation associated with changes in molecular pathways regulating epithelial differentiation such as PTEN signaling and accompanied by induction of cancer-related AJC genes. Genome-wide co-expression analysis identified a smoking-sensitive AJC transcriptional network. The overall expression of AJC-associated genes was further decreased in COPD smokers (n=23). Exposure of human airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC-related genes, accompanied by decreased transepithelial resistance. Thus, cigarette smoking alters the AJC gene expression architecture in the human airway epithelium, providing a molecular basis for the dysregulation of airway epithelial barrier function during the development of smoking-induced lung disease. The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. In this study, microarray analysis of the SAE obtained from 53 healthy nonsmokers, 59 healthy smokers, and 23 smokers with COPD was performed to determine physiological AJC gene expression architecture in the SAE and its modification by cigarette smoking and during the development of COPD.
2011-06-27 | E-GEOD-20257 | biostudies-arrayexpress