Identification of miRNAs in Mouse lung epithelial cells (MLE12) expression of which is altered by exposure to cigarette-smoke extracts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE131188 | GEO | 2020/05/01
REPOSITORIES: GEO
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Project description:normal human bronchial epithelial cultures from two cultures in parallel exposed to cigarette smoke (CS) or air (mock) at timepoints 4 hours and 24 hours. Keywords = cigarette smoke Keywords = microarray Keywords = bronchial cell Keywords = tobacco Keywords: time-course
2005-02-23 | GSE2302 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is currently the third cause of death worldwide with still increasing mortality and morbidity. Primary etiology of COPD is cigarette smoking. However, in clinic, not all smokers develop COPD. The underlying mechanism remains unclear. A549 cells, which are widely used in vitro as a model of alveolar type II pulmonary epithelium, were subjected to step-wise increasing cigarette smoke extract (CSE) treatments. Those cigarette smoke extract resistant (SER) cells were cultured and used for further experiments. The aim of this study is to investigate the differentially expressed genes in SER group with or without CSE treatment and identify potential genes or pathways which could play a role in COPD pathogenesis.
2024-01-01 | GSE222965 | GEO
Project description:Proteasome dysfunction is emerging as a novel pathomechanism for the development of chronic obstructive pulmonary disease (COPD), a major leading cause of death in the world. Cigarette smoke is one of the main risk factors for COPD and has been shown to impair proteasome function in vitro and in vivo. Importantly, proteasome activity is inhibited in COPD lungs while expression levels of proteasome subunits are not altered. In the present study, we dissected the molecular changes induced by cigarette smoke on proteasome function in lung epithelial cells and mouse lungs. We analyzed the integrity, composition, and the interactome of isolated 26S proteasome complexes from smoke-exposed cells and mouse lungs. Moreover, we applied native MS analysis to investigate whether reactive compounds of cigarette smoke directly modify and inhibit the 20S proteasome complex. Our data reveal that the 20S proteasome is slightly destabilized in the absence of any dominant modification of proteasomal proteins. 26S pulldown and stoichiometry analysis indicated that 26S proteasome complexes become instable in response to cigarette smoke exposure. Of note, the interactome of the 26S was clearly altered in smoke-exposed mouse lungs possibly reflecting an altered cellular composition in the lungs of the smoke-exposed mice. Taken together, our results suggest that cigarette smoke induces minor but detectable changes in the stability and interactome of 20S and 26S proteasome complexes which might contribute in a chronic setting to imbalanced proteostasis as observed in chronic lung diseases associated with cigarette smoking.
2019-01-08 | PXD007148 | Pride
Project description:Cigarette smoking is the major cause of chronic inflammatory diseases such as Chronic Obstructive Pulmonary Disease (COPD). It is paramount to develop pharmacological interventions and delivery strategies against the cigarette smoke (CS) associated oxidative stress in COPD. This study in Wistar rats examined cysteamine in nanoemulsions to counteract the cigarette smoke distressed microenvironment. In vivo, 28 days of cigarette smoke and 15 days of cysteamine nanoemulsions treatment starting on 29th day consisting of oral and inhalation routes were established in Wistar rats. Additionally, we conducted inflammatory and epithelial-to-mesenchymal transition (EMT) studies in vitro in human bronchial epithelial cell lines (BEAS2B) using 5% cigarette smoke extract. Inflammatory and anti-inflammatory markers such as TNF-α, IL-6, IL-1ß, IL-8, IL-10, IL-13, have been quantified in bronchoalveolar lavage fluid (BALF) to evaluate the effects of the cysteamine nanoemulsions in normalizing the diseased condition. Histopathological analysis of the alveoli and the trachea showed the distorted, lung parenchyma and ciliated epithelial barrier, respectively. To obtain mechanistic insights into the cigarette smoke COPD rat model, “shotgun” proteomics of the lung tissues have been carried out using high-resolution mass spectrometry wherein genes such as ABI1, PPP3CA, PSMA2, FBLN5, ACTG1, CSNK2A1, and ECM1 exhibited significant differences across all the groups. Pathway analysis showed autophagy, signaling by receptor tyrosine kinase, cytokine signaling in immune system, extracellular matrix organization, and hemostasis, as the major contributing pathways across all the studied groups. This work offers new preclinical findings on how cysteamine taken orally or inhaled can combat cigarette smoke-induced oxidative stress.
2023-08-21 | PXD033529 | Pride
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:BACKGROUND: The HHIP gene, encoding Hedgehog interacting protein, has been implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS), and our subsequent studies identified a functional upstream genetic variant that decreased HHIP transcription. However, little is known about how HHIP contributes to COPD pathogenesis. METHODS: Here, we exposed Hhip haploinsufficient mice (Hhip+/-) to cigarette smoke (CS) for 6 months to model the biological consequences caused by CS in human COPD risk-allele carriers at the HHIP locus. Gene expression profiling in murine lungs was performed followed by an integrative network inference analysis, PANDA (Passing Attributes between Networks for Data Assimilation) analysis. RESULTS: We detected more severe airspace enlargement in Hhip+/- mice vs. wild-type littermates (Hhip+/+) exposed to CS. Gene expression profiling in murine lungs suggested enhanced lymphocyte activation pathways in CS-exposed Hhip+/- vs. Hhip+/+ mice, which was supported by increased numbers of lymphoid aggregates and enhanced activation of CD8+ T cells after CS-exposure in the lungs of Hhip+/- mice compared to Hhip+/+ mice. Mechanistically, results from PANDA network analysis suggested a rewired and dampened Klf4 signaling network in Hhip+/- mice after CS exposure. CONCLUSIONS: In summary, HHIP haploinsufficiency exaggerated CS-induced airspace enlargement, which models CS-induced emphysema in human smokers carrying COPD risk alleles at the HHIP locus. Network modeling suggested rewired lymphocyte activation signaling circuits in the HHIP haploinsufficiency state. Total RNA was obtained from the lung tissue of C57BL/6J mice exposed to cigarette smoke (CS) or filtered air (air) for 6 months. Six mice from each of four groups with different genotypes (Hhip+/+ or Hhip+/-) and treatments (air or CS) were randomly chosen for gene expression profiling
2015-01-21 | E-GEOD-65124 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
2016-01-01 | GSE57073 | GEO
Project description:Although cigarette smoke (CS) is the primary risk factor for COPD, the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6J, NZW/LacJ) and two genetic models with mutations in COPD GWAS genes (HHIP, FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene response patterns that correlate with severity of emphysema in mouse and human lungs. Xenobiotic metabolism and Nrf2-mediated oxidative stress response were commonly regulated molecular response patterns across C57BL/6J, Hhip +/- and Fam13a -/- murine models upon chronic CS exposure and human COPD subjects. The CS resistant Fam13a -/- mouse and NZW/LacJ strain revealed an opposite pattern of gene expression response, suggesting distinct molecular pathways for resistance against emphysema. There were few genes commonly modulated between mouse and humans. Our study suggests gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS
2017-09-05 | GSE87292 | 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
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.
2014-12-04 | GSE52509 | GEO