Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE180651 | GEO | 2021/08/13
REPOSITORIES: GEO
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Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD. Lung tissue from smokers with no evidence of obstructive lung disease and smokers with COPD was examined for miRNA and mRNA expression followed by validation. We then examined both miRNA and mRNA expression to enrich for relevant biological pathways
2012-06-26 | E-GEOD-38974 | biostudies-arrayexpress
Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD.
2012-06-27 | GSE38974 | GEO
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
2022-05-23 | GSE183974 | GEO
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
2022-05-23 | GSE183973 | GEO
Project description:Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders. MicroRNA profiling identified 34 miRNAs up-regulated by cigarette smoking in human small airway epithelium. Even after quitting smoking for 3 months, 12 miRNAs didnât return to normal level.
2015-11-23 | E-GEOD-53519 | biostudies-arrayexpress
Project description:Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders.
2015-11-23 | GSE53519 | 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:Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients
| PRJNA749028 | ENA
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:Rationale: COPD is characterized by an abnormal regulatory T cell (Treg) response and increases in Th1 and Th17 cell responses. It is unclear if dysregulation of miRNAs within Treg alters the adaptive immunophenotype in COPD. Objectives: To compare the miRNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed miRNAs. Methods: Treg cells (CD4+CD25+CD49-CD127-) and T effector (CD4+CD25-) cells were obtained from the peripheral blood of 4 nonsmokers, 4 healthy current smokers, and 4 COPD current smokers for analysis of miRNA expression, matching them for age and sex. We assessed expression initially by microarray analysis on the Illumina miRNA platform then conducted real time RT-PCR validation of the microarray results. 24 samples were analyzed. 8 from each patient group of healthy Normal, Healthy Smoker, and COPD Smoker.
2014-04-19 | E-GEOD-56923 | biostudies-arrayexpress