Muti-omic analysis of long-term particulate matter-induced pulmonary injury
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ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Tianyu Zhou
PROVIDER: PXD030874 | iProX | Tue Jan 11 00:00:00 GMT 2022
REPOSITORIES: iProX
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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression
2007-12-01 | GSE9465 | GEO
Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon DNA was extracted and anlyzed. Genome-wide DNA methylation profiles were determinen. DNA amplicons were prepared using Differential Methylation Hybridization (DMH) method, subsequently hybridized on to the Customized Agilent Rat CpG island Microarray. The goal was to unravel the DNA methylation patterns in different subgropus of tendon tissue according to partciulate matter exposure.
2022-08-03 | GSE200709 | GEO
Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon RNA was extracted and anlyzed.
2022-08-03 | GSE200463 | GEO
Project description:Background Airborne fine particulate matter with diameter < 2.5 μm (PM2.5), can reach the alveolar regions of the lungs, and is associated with over 4 million premature deaths per year worldwide. However, the source-specific consequences of PM2.5 exposure remain poorly understood. A major, but unregulated source is car brake wear, which exhaust emission reduction measures have not diminished.AQ1 Methods We used an interdisciplinary approach to investigate the consequences of brake-wear PM2.5 exposure upon lung alveolar cellular homeostasis using diesel exhaust PM as a comparator. This involved RNA-Seq to analyse global transcriptomic changes, metabolic analyses to investigate glycolytic reprogramming, mass spectrometry to determine PM composition, and reporter assays to provide mechanistic insight into differential effects. Results We identified brake- wear PM from copper-enriched non-asbestos organic, and ceramic brake pads as inducing the greatest oxidative stress, inflammation, and pseudohypoxic HIF activation (a pathway implicated in diseases associated with air pollution exposure, including cancer, and pulmonary fibrosis), as well as perturbation of metabolism, and metal homeostasis compared with brake wear PM from low- or semi-metallic pads, and also, importantly, diesel exhaust PM. Compositional and metal chelator analyses identified that differential effects were driven by copper. Conclusions We demonstrate here that brake-wear PM may perturb cellular homeostasis more than diesel exhaust PM. Our findings demonstrate the potential differences in effects, not only for non-exhaust vs exhaust PM, but also amongst different sources of non-exhaust PM. This has implications for our understanding of the potential health effects of road vehicle-associated PM. More broadly, our findings illustrate the importance of PM composition on potential health effects, highlighting the need for targeted legislation to protect public health.
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Project description:RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by air polution particulate matter (PM) in macrophages. We therefore sought to determine the effect of both exogenous itaconate (4-octyl itaconate) and endogenous itaconate on PM-induced inflammation in macrophages through RNA sequencing.
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Project description:Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure; The mechanistic link between human exposure to airborne particulate matter (PM) pollution and the increased cardiovascular morbidity and mortality observed in people with congestive heart failure (CHF) is unknown. We now show that exposure of genetically-engineered mice with CHF (expressing a cardiac-specific CREB mutant transcription factor) to ambient PM (collected in Baltimore, mean aerodynamic diameter 1.9 um) unmasks severe autonomic morbidities manifested as significant reductions in heart rate variability, respiratory dysynchrony and increased frequency of serious ventricular arrhythmias, features not observed in PM-challenged wild type mice without CHF. PM exposure in CREB mice with CHF reflexly triggers autonomic dysfunction via heightened carotid body function as evidenced by pronounced afferent nerve responses to hypoxia and marked depression of breathing by hyperoxia challenge. Genomic analyses of lung and ventricular tissues revealed PM-induced molecular signatures of inflammation and oxidative stress. These findings in a murine model of cardiac failure provide the first direct assessment of autonomic function in response to PM challenge and are highly consistent with current epidemiologic findings on cardiovascular morbidity in susceptible PM-exposed human populations. We utilized a murine model of dilated cardiomyopathy to address potential mechanistic links between PM exposure and the development of life-threatening cardiac dysrhythmias. Experiment Overall Design: four group (n=3) of animals were treated by PBS or particulate matter (20mg/kg 1.9µm particulate matter) in Wild type or CD-1 dominate negative mice
2009-08-15 | E-GEOD-17478 | biostudies-arrayexpress
Project description:Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure The mechanistic link between human exposure to airborne particulate matter (PM) pollution and the increased cardiovascular morbidity and mortality observed in people with congestive heart failure (CHF) is unknown. We now show that exposure of genetically-engineered mice with CHF (expressing a cardiac-specific CREB mutant transcription factor) to ambient PM (collected in Baltimore, mean aerodynamic diameter 1.9 um) unmasks severe autonomic morbidities manifested as significant reductions in heart rate variability, respiratory dysynchrony and increased frequency of serious ventricular arrhythmias, features not observed in PM-challenged wild type mice without CHF. PM exposure in CREB mice with CHF reflexly triggers autonomic dysfunction via heightened carotid body function as evidenced by pronounced afferent nerve responses to hypoxia and marked depression of breathing by hyperoxia challenge. Genomic analyses of lung and ventricular tissues revealed PM-induced molecular signatures of inflammation and oxidative stress. These findings in a murine model of cardiac failure provide the first direct assessment of autonomic function in response to PM challenge and are highly consistent with current epidemiologic findings on cardiovascular morbidity in susceptible PM-exposed human populations. We utilized a murine model of dilated cardiomyopathy to address potential mechanistic links between PM exposure and the development of life-threatening cardiac dysrhythmias.
2009-08-10 | GSE17478 | GEO
Project description:Chronic exposure to ambient particulate matter (PM) increases the risk of cardiovascular disease (CVD). One proposed mechanism linking PM exposure and CVD is the induction of low-grade systemic inflammation that underlies disease progression. However, the intermediaries that relay signals from the proximal sites of inflammation to the periphery remain unknown. We have previously shown that fine PM (PM2.5) alter red blood cell distribution width. Therefore, the overall goal of this study was to elucidate how PM exposure impacts the spleen and splenic macrophages which are primarily responsible for the turnover of aged and damaged red blood cells.
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Project description:The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group).PM2.5 at 150 μg/m3were administered by intratracheal instillation during the gestation period of female rats from Day 1 of conception onwards.After the female rat gave birth,the offspring's heart DNA was extracted and anlyzed. DNA promotor methylation profile were determined.The goal was to determine the effects of PM2.5 exposure on the DNA promotor methylation patterns in heart tissue.
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