Transcriptional adaptation of human airway epithelium upon cigarette smoking
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237252 | GEO | 2025/08/10
REPOSITORIES: GEO
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Project description:Smoking is the leading cause of preventable death worldwide. It increases the risk for various diseases including respiratory diseases, vascular diseases and different cancers including lung, oral and bladder cancer. Despite being the leading cause of oral cancer, the molecular mechanisms resulting in malignancy upon cigarette smoke exposure are yet to be fully elucidated. It is crucial to note that disease development is observed upon chronic exposure to cigarette smoke, as opposed to a short-term exposure. Hence, we sought to investigate the effect of chronic smoke exposure on normal oral keratinocytes (OKF6/TERT1). We employed tandem mass tag-based quantitative proteomic and phosphoproteomic approaches to investigate the proteomic and signaling changes in OKF6/TERT1 cells chronically exposed to cigarette smoke compared to untreated cells. LC/MS2 analysis resulted in the quantification of 5,067 proteins among which expression of 360 proteins were found to be dysregulated in at least one replicate. Phosphoproteomic analysis revealed quantification of 3,647 phosphopeptides corresponding to 1,801 proteins. Majority of the dysregulated proteins were seen to be involved in cellular processes such as cell growth, cellular communication and energy metabolism. This study will aid in elucidating the effects of smoking in oral cancer and in the identification of potential candidates molecules which could serve as early detection biomarkers or therapeutic targets.
2018-03-05 | PXD007637 | Pride
Project description:To study the effect of cigarette smoke exposure on Sars-Cov2 infection, we directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We set out to examine the underlying mechanisms governing the increased susceptibility of cigarette smoke exposed ALI cultures to SARS-CoV-2 infection by usingle cell profiling of the cultures, which showed that interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response.
2020-11-17 | GSE161089 | GEO
Project description:Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly, the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures. We have used cultures from four individual donors, and compared the effects of repeated cigarette smoke challenge (30mins exposure on four separate days), with no challenge.
2011-08-30 | E-GEOD-30660 | biostudies-arrayexpress
Project description:Cigarette smoke is a major risk factor for the development and progression of chronic obstructive pulmonary disease. Tobacco smoking is also the main cause of lung cancer and the main preventable cause of other lung and heart disease. Strategies to eliminate cigarette smoking have led to the emergence of new tobacco-related products as alternatives for cigarette smoking or tools for smoking cessation. Electronic cigarettes (E-cigarettes) have been introduced to the market in recent years as an alternative to smoking conventional cigarettes. E-cigarettes are nicotine delivery devices by heating and converting to aerosol a liquid mixture composed of propylene glycol, vegetable glycerine, flavouring chemicals, and nicotine. Despite the lack of appropriate studies, e-cigarettes are nowadays widely used and advertised as safe cigarette replacements and the number of users is rapidly growing. Unlike cigarette smoke, where the determinant effects are well studied and documented, very limited amount of research has been done on the health effects and public health of e-cigarettes. The study aims to investigate the effects of e-cigarette vapour extract on gene expression in different primary isolated mouse lung cells [pulmonary arterial smooth muscle cells (PASMC) and alveolar epithelial type two cells (AECII)]. The cells will be exposed to e-cigarette vapour extract (ECVE).
2023-05-01 | GSE202215 | GEO
Project description:Smoking is the leading cause of lung cancer death, although only a small percentage of smokers develop the disease. Cigarette smoke exposure is known to cause a field of injury in cells throughout the respiratory tract, and while these airway epithelial cells are morphologically normal, they can undergo genetic alterations in response to cigarette smoke exposure. We used microarrays to analyze the gene expression of epithelial cells in the extrathoracic epithelium, specifically nasal and buccal epithelium, to see if these cells underwent similar genetic alterations in response to tobacco exposure as seen in bronchial epithelial cells as has been previously reported. Keywords: cross sectional
2008-07-03 | GSE8987 | GEO
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
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.
2011-06-27 | GSE20257 | GEO
Project description:BACKGROUND: We have previously reported gene expression changes in the bronchial airway epithelium of active chronic smokers. In this study, we investigate the effects of Acute Smoke Exposure (ASE) from cigarettes on airway epithelial gene expression. METHODS: Bronchial airway epithelial cell brushings were collected via fiberoptic bronchoscopy from 63 individuals without recent exposure to cigarette smoke (> 2 days), at baseline and at 24 hours after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. Differential gene expression was assessed using linear modeling and compared to previous smoking-related gene-expression signatures using Gene Set Enrichment Analysis (GSEA). RESULTS: We identified 91 genes differentially expressed 24-hours after exposure to three cigarettes (FDR < 0.25). ASE induces genes involved in xenobiotic metabolism, oxidative stress, and inflammation; and represses genes involved in cilium morphogenesis, and cell cycle. Genes induced by in vivo ASE are concordantly altered by ASE in vitro. While many genes altered by ASE are altered similarly in the airway of chronic smokers, metallothionein genes were induced by ASE and suppressed among chronic smokers. Metallothioneins were also suppressed in the bronchial airway of current and former chronic smokers with lung cancer relative to those with benign disease. CONCLUSIONS: Acute exposure to as little as three cigarettes alters gene-expression in bronchial airway epithelium in a manner that largely resembles the changes seen in chronic active smokers. The difference in the short-term and long-term effects of smoking on metallothionein expression and its relationship to lung cancer requires further study given these enzymes’ role in responding to oxidative stress.
2018-06-26 | GSE97010 | GEO
Project description:Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans. Here we generated small airway-on-a-chip microdevices lined by living human bronchiolar epithelium from normal or COPD patients and connected them to an instrument that 'breathes' whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. We used microarrays to detail the global program of gene expression in well-differentiated epithelial cells following smoke exposure to recapitulate clinical pathologies and identify disease-specific responses.
2016-09-20 | GSE87098 | GEO
Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with high mortality rate. Smoking is one of the established risk factors of ESCC. However, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. Understanding the effects of cigarette smoke on esophageal squamous epithelial cells at a molecular level would lead to a better understanding of the pathobiology of ESCC which has implications for identification of early biomarkers and therapeutic targets. To investigate the effect of cigarette smoke exposure, we developed a cell line model where Het1A cells (non-neoplastic human esophageal epithelial cells) were chronically treated with cigarette smoke condensate (CSC) for 2 months, 4 months, 6 months and 8 months. We carried out comparative proteomic, phosphoproteomic and whole exome sequencing analyses on CSC treated and untreated cells. Increased cell proliferation and invasion of Het1A cells was observed after chronic exposure to cigarette smoke. Using quantitative proteomic and phosphoproteomic analyses, we identified 56 proteins and 296 phosphoproteins that showed differential expression. Bioinformatics analysis of differentially expressed proteins and phosphoproteins showed enrichment of molecules involved in DNA damage response pathway. Whole exome sequencing (WES) of CSC treated and untreated cells also revealed mutations and copy number alterations in genes associated with DNA damage response. By correlating WES, proteomic and phosphoproteomic results, we observed potential loss of function in HMGN2 and MED1 that were reported as potential tumor suppressors and are known to play important role in DNA damage response. We also observed decreased expression of HMGN2 in tissue section of ESCC. Overexpression of HMGN2 and MED1 lead to decreased proliferative and invasive ability of CSC treated cells. These findings suggest that cigarette smoke affects genes and proteins associated with DNA damage response pathways which might play a vital role in development of ESCC.
2021-09-07 | PXD007799 | Pride