Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease [methylation]
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ABSTRACT:
PROVIDER: PRJNA741119 | ENA |
REPOSITORIES: ENA
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Project description:Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease
| PRJNA741116 | ENA
Project description:Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease [RNA-seq]
| PRJNA741118 | ENA
Project description:Purpose:To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Methods: Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (n=76) were profiled for DNA methylation and gene expression. We evaluated global Alu and LINE-1 methylation and calculated the epigenetic age using the Horvath clock and the methylation telomere length estimator. To identify genome-wide differential DNA methylation and gene expression associated with HIV and COPD, robust linear models were used followed by an expression quantitative trait methylation (eQTM) analysis. Results:Epigenetic age acceleration and shorter methylation estimates of telomere length were found in PLWH with COPD compared to PLWH without COPD and uninfected patients with and without COPD. We identified CpG sites, genes, and eQTM-gene pairs associated with the interaction between HIV and COPD. Conclusions: Methylation age acceleration is observed in the airway epithelium of PLWH with COPD, a process that may be responsible for the heightened risk of COPD in this population. Their distinct methylation profile, differing from that observed in patients with COPD alone, suggests a unique pathogenesis to HIV-associated COPD that warrants investigation into the candidate genes identified.
2022-03-18 | GSE178808 | GEO
Project description:Purpose:To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Methods: Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (n=76) were profiled for DNA methylation and gene expression. We evaluated global Alu and LINE-1 methylation and calculated the epigenetic age using the Horvath clock and the methylation telomere length estimator. To identify genome-wide differential DNA methylation and gene expression associated with HIV and COPD, robust linear models were used followed by an expression quantitative trait methylation (eQTM) analysis. Results:Epigenetic age acceleration and shorter methylation estimates of telomere length were found in PLWH with COPD compared to PLWH without COPD and uninfected patients with and without COPD. We identified CpG sites, genes, and eQTM-gene pairs associated with the interaction between HIV and COPD. Conclusions: Methylation age acceleration is observed in the airway epithelium of PLWH with COPD, a process that may be responsible for the heightened risk of COPD in this population. Their distinct methylation profile, differing from that observed in patients with COPD alone, suggests a unique pathogenesis to HIV-associated COPD that warrants investigation into the candidate genes identified.
2022-03-18 | GSE178807 | GEO
Project description:Rationale: Age-related diseases like chronic obstructive pulmonary disease (COPD) occur at higher rates in people living with human immunodeficiency virus (PLWH) than in uninfected populations. Objectives: To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Methods: Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (N = 76) were profiled for DNA methylation and gene expression. We evaluated global Alu and LINE-1 methylation and calculated the epigenetic age using the Horvath clock and the methylation telomere length estimator. To identify genome-wide differential DNA methylation and gene expression associated with HIV and COPD, robust linear models were used followed by an expression quantitative trait methylation (eQTM) analysis. Measurements and Main Results: Epigenetic age acceleration and shorter methylation estimates of telomere length were found in PLWH with COPD compared with PLWH without COPD and uninfected patients with and without COPD. Global hypomethylation was identified in PLWH. We identified 7,970 cytosine bases located next to a guanine base (CpG sites), 293 genes, and 9 expression quantitative trait methylation-gene pairs associated with the interaction between HIV and COPD. Actin binding LIM protein family member 3 (ABLIM3) was one of the novel candidate genes for HIV-associated COPD highlighted by our analysis. Conclusions: Methylation age acceleration is observed in the airway epithelium of PLWH with COPD, a process that may be responsible for the heightened risk of COPD in this population. Their distinct methylation profile, differing from that observed in patients with COPD alone, suggests a unique pathogenesis to HIV-associated COPD. The associations warrant further investigation to establish causality.
| S-EPMC9887412 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-18 | GSE178809 | GEO
Project description:We report that the canonical WNT pathway is upregulated in the proximal epithelium of patients with chronic obstructive pulmonary disease. Our data were obtained by using redifferentiated airway epithelium in air/liquid interface, and sequencing the transcriptional activity of components of the WNT signalling pathway
2020-08-04 | GSE155588 | GEO
Project description:To profile airway and parenchyma transcriptomes in our mouse model of asthma chronic obstructive pulmonary disease overlap, we employed RNA-Seq (TruSeq Stranded mRNA sample preparation, NovaSeq 6000, 20 million 100 bp single reads) as a discovery tool to identify mRNAs of interest in the development of experimental asthma chronic obstructive pulmonary disease overlap. Experimental asthma: Some mice were sensitized and challenged intranasally with house dust mite (HDM) extract 5 days per week for 3 weeks. In other mice, this was HDM treatment 3 times/week from weeks 4-11. Controls received phosphate buffered saline (PBS). Experimental chronic obstructive pulmonary disease (COPD): Mice were exposed to cigarette smoke (CS) twice per day, 5 days per week for 8 weeks. Control mice were exposed to normal air (AIR). Experimental asthma-COPD overlap (ACO): Mice were sensitized and challenged intranasally with HDM or PBS. From weeks 4-11, mice were also exposed to CS or AIR. Treatment with dexamethasone (DEX): Separate groups of mice were treated with DEX during week 11. Lungs were excised, airway and parenchyma tissue were isolated through blunt dissection, and total RNA isolated.
2023-02-01 | GSE199853 | GEO
Project description:<p>The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD by an in-depth profiling of sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals. Multi-omic data were integrated using a sequential mediation analysis, to assess in silico associations of the microbiome with neutrophilic or eosinophilic inflammation, two primary COPD inflammatory endotypes, mediated through microbial metabolic interaction with host gene expression. Mechanistic links of microbiome-metabolite-host interaction were identified leveraging microbial genetic information and established metabolite-human gene pairs. The strongest link for neutrophil-predominant COPD was altered tryptophan metabolism driven by airway lactobacilli resulting in reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host IL-22 signaling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema, and lung function decline, via IL-22-mediated macrophage-epithelial cell crosstalk. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.</p><p><br></p><p><strong>Linked studies:</strong></p><p><strong>UPLC-MS/MS assays</strong> of original cohort human samples are reported in this study.</p><p><strong>UPLC-MS/MS assays</strong> of more recent cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS5423' rel='noopener noreferrer' target='_blank'><strong>MTBLS5423</strong></a>.</p><p><strong>UPLC-MS/MS assays</strong> of more recent murine samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6894' rel='noopener noreferrer' target='_blank'><strong>MTBLS6894</strong></a>.</p>
2022-06-20 | MTBLS4017 | MetaboLights
Project description:The proximal-distal patterning program determines unique structural and functional properties of proximal and distal airways in the adult lung. Based on the knowledge that remod-eling of distal airways is the major pathologic feature of chronic obstructive pulmonary disease (COPD), and that small airway epithelium (SAE), which covers distal airways, is the primary site of the initial smoking-induced changes relevant to COPD pathogenesis, we hypothesized that in COPD smokers, the SAE transcriptome loses its region-specific biologic identity and takes on the transcriptional pattern of the proximal airways. By analyzing human airway epithelium col-lected by bronchoscopic brushings from proximal and distal airways of healthy smokers, proxi-mal and distal airway epithelial transcriptome signatures were identified. Dramatic smoking-dependent suppression of distal signature paralleled by acquisition of the proximal airway epithe-lial phenotype was found in the SAE of COPD smokers. Distal-proximal re-patterning observed in the SAE of smokers in vivo was reproduced in vitro by stimulating SAE basal cells (BC), the stem/progenitor cells of the SAE, with EGF, a growth factor up-regulated in airway epithelium by smoking. Together, this study identifies distal-proximal SAE re-patterning as a characteristic feature of small airway disordering in COPD smokers potentially driven by EGF/EGFR-mediated reprogramming of SAE BC stem/progenitor cells.
2017-07-18 | GSE64614 | GEO