Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments
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ABSTRACT:
PROVIDER: PRJNA899045 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22215700_1.fastq.gz | Fastqsanger.gz | |||
| SRR22215700_2.fastq.gz | Fastqsanger.gz | |||
| SRR22215701_1.fastq.gz | Fastqsanger.gz | |||
| SRR22215701_2.fastq.gz | Fastqsanger.gz | |||
| SRR22215702_1.fastq.gz | Fastqsanger.gz |
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Project description:Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.
2023-05-31 | GSE217456 | GEO
Project description:Particulate matter (PM) exposure and metabolic syndrome (MetSyn) coexist in both industrialized and developing nations. PM and MetSyn are strong risk factors for chronic obstructive pulmonary disease (COPD) and asthma. After the World Trade Center collapse in 9/11/2001, PM-exposed individuals from the Fire Department of New York City (FDNY) developed a progressively lung disease. This nested case-cohort study is composed of never smoking, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. Representative cohort controls with serum drawn within six months of 9/11 (n=100). FEV1 at subspecialty exam defined cases: susceptible World Trade Center Lung Injury (WTC-LI) cases (n=50) had FEV1< lower limit of normal (LLN) and resistant WTC-LI cases with FEV1 ≥107% predicted (n=50). This study will determine the metabolomics profile that differentiates firefighters with WTC-LI, firefighters resistant to WTC-LI, and similarly exposed cohort controls.
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Project description:Posttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.
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Project description:Gene expression has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD), but specific regulatory transcriptomic mechanisms remain unknown. The current study addressed this limitation by analyzing transcriptome-wide RNA-Seq of whole blood samples from N=226 World Trade Center responders. The investigation focused on differential expression (DE) at gene, isoform, and alternative splicing (AS) levels associated with Posttraumatic Stress Disorder symptoms: total burden and its re-experiencing, avoidance, numbing, and hyperarousal subdimensions; and is the first study to characterize the AS landscape in PTSD. These dimensions were associated with 76, 1, 48, 15, and 49 genes, respectively (FDR<0.05). Similarly, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with regard to DE genes, isoforms and AS correlates. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications for the treatment of PTSD. Overall, findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at gene and AS levels. The DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.
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Project description:The gene expression approach has provided promising insights into the pathophysiology of PTSD. However, few studies used hypothesis-free transcriptome-wide expression approach. Transcriptome-wide expression study using RNA sequencing (RNA-Seq) of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current and 42 past PTSD). The current and never PTSD samples were randomly split to form both discovery (N=195) and replication (N=87) cohorts. Differentially expressed genes identified in RNA-Seq were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, and 5 (FKBP5, NDUFA1, CCDC85B, SNORD54, SNORD46) showed >1.2-fold difference in expression consistently between the discovery and replication cohorts. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but were not significant following FDR correction. The gene expression score achieved sensitivity of 0.917 and specificity of 0.508 for identifying PTSD cases in the replication cohort. It was similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls. We confirmed the role of FKBP5 in PTSD and identified four additional differentially expressed genes that may constitute biomarkers for this condition. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.
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Project description:Here we used next generation sequencing (NGS), to determine the transcriptional profile of blood cells exposed to particulate matter to contribute to the clarification of the importance of deregulated molecules in the molecular pathways involved in the inflammation. For this, blood cells from six adult healthy donors were treated with particulate matter.
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Project description:This study aimed to shed light on the gene regulatory networks underlying plant leaf responses to air particulate matter. Our investigation focused on autochthonous shrubs of laurel (Laurus nobilis L.) grown in pots located in two contrasting areas: a highly polluted traffic road and rural countryside within the same town (Altopascio, Lucca, Italy). RNA-seq data were related to leaf morphological traits and air particulate matter, allowing to identify key players in modulating the capabilities of plants to phyllo-remediate high air particulate matter levels in urban environment.
2023-03-16 | E-MTAB-12332 | biostudies-arrayexpress
Project description:Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-PET), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flow-velocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M post-exposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after PM-exposure. Similarly, α-smooth muscle actin(α-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. Our study shows persistent WTC-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after PM exposure. Early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets.
| S-EPMC7035300 | biostudies-literature