Gene expression profiling of lung organoids at CSD5, CSD14, and ND14 stages.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE324112 | GEO | 2026/03/15
REPOSITORIES: GEO
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Project description:<p>Background: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disorder with rising global morbidity and mortality. Emerging evidence suggests that systemic metabolic alterations, particularly dyslipidemia, contribute to COPD pathogenesis. However, the mechanisms linking lipid dysregulation to pulmonary inflammation and tissue injury remain poorly defined.</p><p>Methods: Untargeted metabolomic profiling was performed on plasma samples from healthy individuals and patients with COPD to identify disease associated metabolic alterations. A high-cholesterol diet (HCD) mouse model, with or without chronic cigarette smoke exposure, was used to examine the impact of systemic cholesterol elevation on lung structure and inflammation. Complementary in vitro studies using THP-1 derived and bone marrow derived macrophages were conducted to investigate mitochondrial function, ROS generation, and downstream signaling pathways. Transcriptomic analyses were employed to identify key molecular mediators.</p><p>Results: Plasma metabolomics revealed significant dysregulation of lipid metabolism in COPD, with elevated cholesterol levels correlating inversely with lung function. In vivo, HCD feeding induced pulmonary inflammation and further exacerbated cigarette smoke induced lung tissue destruction. In macrophages, combined cholesterol loading and cigarette smoke extraction treatment disrupted mitochondrial integrity, reduced respiratory capacity, and increase ROS generation. Elevated ROS levels upregulated PPIA, which in turn activated NF-κB signaling and promoted IL-1β secretion. Silencing PPIA or inhibiting ROS significantly attenuated NF-κB activation and cytokine release. Consistent with these findings, increased PPIA expression and NF-κB phosphorylation were observed in lungs of HCD-fed, cigarette smoke exposed mice, and PPIA levels were elevated in bronchoalveolar lavage fluid from COPD patients.</p>
2025-11-26 | MTBLS13388 | MetaboLights
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
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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
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Project description:Lung cancer remains a major contributor to cancer fatalities, with cigarette smoking known to be responsible for up to 80% of cases. Based on the ability of cigarette smoke to induce inflammation in the lungs and increased lung cancer incidence in smokers with inflammatory conditions such as COPD, we hypothesized that inflammation plays an important role in carcinogenicity of cigarette smoke. In order to test this hypothesis, we performed multi-omic analyses of Type II pneumocytes of A/J mice exposed to cigarette smoke for various time periods. We found that cigarette smoke exposure resulted in significant changes in DNA methylation and hydroxymethylation, gene expression patterns, and protein abundance that were partially reversible and contributed to an inflammatory and potentially oncogenic phenotype.
2024-09-18 | GSE275545 | GEO
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: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: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.
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