Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA306914 | ENA |
REPOSITORIES: ENA
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Project description:Enhanced autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the small airway epithelium to identify smoking up-regulated genes known to re-spond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 as significantly up-regulated by smoking in both the large and small airway epithelium (1.8-fold, p<0.01, 2.1-fold, p<10-4, respectively), an observation confirmed by an independent small airway microarray cohort, TaqMan PCR and RNAseq. Genome-wide correlation of RNAseq analysis of airway basal/progenitor cells isolated from healthy subjects (n=17) showed a direct correlation of OSGIN1 mRNA levels to multiple classic autophagy genes, including, LC3B, P62, WIPI1 and ATG13 (all rho>0.7, p<0.01). In vitro cigarette smoke extract exposure of nonsmoker primary airway basal/progenitor cells was accompanied by a dose-dependent up-regulation of OSGIN1 and autophagy induction. Lentivirus-mediated enhanced expression of OSGIN1 in human primary basal/progenitor cells induced puncta-like staining of LC3B and up-regulation of LC3B mRNA and protein and P62 mRNA expression level in a dose and time-dependent manner. OSGIN1-induction of autophagosome / amphistome / autolysosome formation was confirmed by co-localization of LC3B with P62 or CD63 (endosome marker) and LAMP1 (lysosome marker). Induction of autophagy by OSGIN1 is accompanied with heightened oxidative stress. Together, these observations support the concept that smoking-induced up-regulation of OSGIN1 is at least one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium.
2017-08-31 | GSE76326 | GEO
Project description:Enhanced autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the small airway epithelium to identify smoking up-regulated genes known to re-spond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 as significantly up-regulated by smoking in both the large and small airway epithelium (1.8-fold, p<0.01, 2.1-fold, p<10-4, respectively), an observation confirmed by an independent small airway microarray cohort, TaqMan PCR and RNAseq. Genome-wide correlation of RNAseq analysis of airway basal/progenitor cells isolated from healthy subjects (n=17) showed a direct correlation of OSGIN1 mRNA levels to multiple classic autophagy genes, including, LC3B, P62, WIPI1 and ATG13 (all rho>0.7, p<0.01). In vitro cigarette smoke extract exposure of nonsmoker primary airway basal/progenitor cells was accompanied by a dose-dependent up-regulation of OSGIN1 and autophagy induction. Lentivirus-mediated enhanced expression of OSGIN1 in human primary basal/progenitor cells induced puncta-like staining of LC3B and up-regulation of LC3B mRNA and protein and P62 mRNA expression level in a dose and time-dependent manner. OSGIN1-induction of autophagosome / amphistome / autolysosome formation was confirmed by co-localization of LC3B with P62 or CD63 (endosome marker) and LAMP1 (lysosome marker). Induction of autophagy by OSGIN1 is accompanied with heightened oxidative stress. Together, these observations support the concept that smoking-induced up-regulation of OSGIN1 is at least one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium.
2017-08-31 | GSE76324 | GEO
Project description:Role of OSGIN1 in Mediating Smoking-induced Autophagy in the Human Airway Epithelium
| PRJNA306916 | ENA
Project description:Role of OSGIN1 in Mediating Smoking-induced Autophagy in the Human Airway Epithelium [RNA-Seq]
| PRJNA306915 | ENA
Project description:The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 ± 15 pack-yr). Gene expression differences [fold-change >1.5, p< 0.01, Benjamini-Hochberg correction] were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 ± 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly up- and down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate “canary” for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease. Experiment Overall Design: Tracheal gene expression: matched group of small airway epithelial samples (n=23 healthy non-smokers, n= 19 healthy smokers)
2009-09-04 | E-GEOD-13933 | biostudies-arrayexpress
Project description:The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 ± 15 pack-yr). Gene expression differences [fold-change >1.5, p< 0.01, Benjamini-Hochberg correction] were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 ± 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly up- and down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate “canary” for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease.
2009-08-27 | GSE13933 | GEO
Project description:Testican 3 (coded for by SPOCK3), is an extracellular matrix heparan/chondroitin sulphate proteoglycan that possesses serine and cysteine protease inhibitor-like domains Based on the knowledge that serine proteases contribute to the destruction of the lung in cigarette smokers, but that only a fraction of smokers develop smoking-induced lung disease, we hypothesized that smokers expressed SPOCK3 at lower levels in the small airway epithelium, the initial site of smoking-induced disease, and further, that genetic variability modulates the expression of SPOCK3 in the airway epithelium. Assessment of gene expression in the small airway epithelium (10th -12th order bronchi) of healthy non-smokers (n=38) and healthy smokers (n=42), demonstrated that the expression levels of SPOCK3 were significantly lower in healthy smokers compared to healthy nonsmokers (p<0.04). Affymetrix Human SNP array 5.0 was used to assess genome wide single nucleotide polymorphisms (SNPs) within 100 kbp of the SPOCK3 gene in the same nonsmokers and smokers, and these SNPs were correlated with small airway gene expression of SPOCK3, with correction for variation in genetic ancestry. There was a significant correlation of SPOCK3 small airway epithelial gene expression with 13 adjacent SNPs in the SPOCK3 gene (p<10-3, all comparisons, Wald test). For example, the TT allele of rs13124292, located in intron 3, was associated with a small airway epithelial expression levels of 0.56 ± 0.07, and the AA genotype with expression levels of 2.31 ± 0.26 (p<10-6, pairwise t test). Interestingly, smoking appeared to lessen the degree to which genotype associated with SPOCK3 expression level, i.e., smoking to some extent overrode the influence of genetic variation. The observation that SPOCK3 gene expression in the small airway epithelium is reduced in smokers, and that smoking interacts with cis-genomic variations to determine the levels of SPOCK3 small airway epithelial gene expression, is consistent with the concept that everyone is at risk for smoking-induced lung disease, but that inherited genetic variations contribute to the pathogenesis of susceptibility to smoking-induced disease.
2024-06-05 | GSE13932 | 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:The Wnt pathway plays a central role in controlling differentiation of epithelial tissues; when Wnt is on, differentiation is suppressed, but when Wnt is off, differentiation is allowed to proceed. Based on this concept, we hypothesized that expression of key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the differentiated state of the airway epithelium. For this purpose, HG-U133 Plus 2.0 microarrays were used to assess the expression of Wnt-related genes in the small airway (10th-12th generation) epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers (n=47), healthy smokers (n=58), and smokers with established COPD (n=22). With expression defined as present in >20% of samples, microarray analysis demonstrated that 35 of 57 known Wnt-related genes are expressed in the adult SAE. Wnt pathway downstream targets β-catenin (p<0.05) and the transcription factor 7-like 1 were down-regulated in healthy smokers, and smokers with COPD, as were a number of Wnt target genes, including VEGFA, CCND1, MMP7, CLDN1, SOX9, RHOU (all p<0.05 compared to healthy nonsmokers). As a mechanism to explain this broad, smoking-induced suppression of the Wnt pathway, we assessed expression of the DKK and SFRP families, extracellular regulators that suppress the Wnt pathway. Among these, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold (p<0.0001) in healthy smokers and 4.9-fold (p<0.0001) in COPD smokers, an observation confirmed by TaqMan Real-time PCR. AT the protein levels, Western analysis demonstrated SFRP2 up-regulation, and immunohistochemistry demonstrated that the smoking-induced SFRP2 upregulation occurred in differentiated ciliated cells. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and downregulation of Wnt target genes in airway epithelial cells in vitro. These observations are consistent with the hypothesis that the Wnt pathway plays a role in airway epithelial cell differentiation in the adult human airway epithelium, with smoking associated with down-regulation of Wnt pathway, contributing to the dysregulation of airway epithelial differentiation observed in the smoking-related airway disorders. Affymetrix arrays were used to assess gene expression data of genes in the Wnt pathway in small airway epithelium obtained by fiberoptic bronchoscopy of 47 healthy non-smokers and 58 healthy smokers and 22 smokers with COPD.
2011-04-20 | E-GEOD-19407 | biostudies-arrayexpress
Project description:Disparate Oxidant-related Gene Expression of Human Small Airway Epithelium Compared to Autologous Alveolar Macrophages in Response to the In Vivo Oxidant Stress of Cigarette Smoking The oxidant burden of cigarette smoking induces lung cell dysfunction, and play a significant role in the pathogenesis of lung disease. Two cell populations directly exposed to the oxidants in cigarette smoke are the small airway epithelium and alveolar macrophages. Of these, the epithelium appears to be more vulnerable to smoking, becoming disordered in differentiation, repair and function, while alveolar macrophages become activated, without becoming diseased. In this context, we asked: for the same individuals, what is the baseline trancriptome of oxidant-related genes in small airway epithelium compared to alveolar macrophages and do the responses of the transcriptome of these 2 cell populations differ substantially to inhaled cigarette smoke? To address these questions we used microarray gene expression and TaqMan analysis to assess the gene expression profile of known oxidant-related genes in paired samples recovered by bronchoscopy from small airway epithelium and alveolar macrophages from the same healthy nonsmokers and normal smokers. Of the 155 oxidant-related genes surveyed, 122 (77%) were expressed in both cell populations in nonsmokers. However, of the genes expressed by both cell populations, oxidant related gene expression levels were higher in alveolar macrophages (67 genes, 43%) than small airway epithelium (37 genes, 24%). There were more oxidant-related genes uniquely expressed in the small airway epithelium (17%), than in alveolar macrophages (5%). In healthy smokers, the majority of oxidant-related genes were expressed in both cell populations, but there were marked differences in the numbers of oxidant-related genes that smoking up- or down-regulated. While smoking up-regulated 15 genes (10%) and down-regulated 7 genes (5%) in the small airway epithelium, smoking had far less effect on alveolar macrophages [only 4 (3%) genes up-regulated, and only 1 (0.6%) down-regulated]. Only a small number of smoking responsive oxidant-related genes overlapped between the two cell types (2 up-regulated, and no down-regulated genes). Consistent with this observation, pathway analysis of smoking-responsive genes in the small airway epithelium showed oxidant-related pathways dominated, but in alveolar macrophages immune-response pathways dominated. Thus, the responses of the oxidant-related transcriptome of cells with an identical genome and exposed to the same oxidant stress of cigarette smoking are very different, with responses of oxidant-related genes of alveolar macrophages far more subdued than that of small airway epithelium, consistent with the clinical observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to the oxidant stress of cigarette smoking. Gene expression profiles of known oxidant-related genes in paired samples recovered by bronchoscopy from small airway epithelium and alveolar macrophages from the same healthy nonsmokers and normal smokers.
2011-09-11 | E-GEOD-13931 | biostudies-arrayexpress