Serum Exosomal miRNA Signature in occupational medicamentosa-like dermatitis induced by trichloroethylene
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247297 | GEO | 2023/11/13
REPOSITORIES: GEO
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Project description:To know if Trichloroethylene (TCE) can induce miRNA expression changes in mouse liver, we use microarray to screen for differentially expressed miRNAs in the liver of mice exposed to TCE at a dose of 1000 mg/kg b.w. for 5days . In our results, nine miRNAs were selected by volcano plot filtering (fold change ≥ 2 and P-value ≤ 0.05), out of which eight were up-regulated and one was down-regulated. The differential expression of miR-182-5p, miR-34a-5p and miR-451a were validated by qPCR.
2016-11-22 | GSE85904 | GEO
Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance. 16 mouse strains were studied, vehicle control and mice treated by gavage with 2100 mg/kg Trichloroethylene and sacrificed 24 hrs after dosing
2011-02-01 | E-GEOD-24278 | biostudies-arrayexpress
Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance.
2011-02-01 | GSE24278 | GEO
Project description:Purpose: Trichloroethylene (TCE) and tetrachloroethylene (PCE) are ubiquitous environmental contaminants and occupational health hazards. The goals of this study were to establish the common and differing transcriptional effects of TCE and PCE. This study examined liver and kidney effects of TCE and PCE in a dose-response study design. Methods: Equi-molar doses of TCE (24, 80, 240, 800 mg/kg) or PE (30, 100, 300, 1,000 mg/kg) were administered by gavage in aqueous vehicle to male B6C3F1/J mice. Tissues were collected 24 hrs after exposure. Trichloroacetic acid (TCA), a major oxidative metabolite of both compounds, was measured and RNA sequencing was performed on liver and kidney samples, with ~30 samples for each organ (29 after QC). Results: Most dose-responsive pathways were common among chemicals/tissues, with the strongest effect on peroxisomal beta-oxidation. Effects on liver and kidney mitochondria-related pathways were notably unique to PCE. Tissue-specific acute transcriptional effects of TCE and PCE occurred at human equivalent doses comparable to those for apical effects. Conclusions: Our study is the first RNA-Seq transcriptional study of TCE vs. PCE in both liver and kidney, enabling a detailed comparison of the chemicals and effects on different organs. Our results show strong commonalities of effects, although PCE shows stronger transcriptional responses than TCE for the same equimolar doses.
2017-07-06 | GSE100296 | GEO
Project description:To examine changes, if any, in the expression of mRNAs in the liver tissue of mice, we have employed whole genome microarray expression profiling as a discovery platform to identify genes responsive to Trichloroethylene (TCE) treatment. In our results, the expression levels of 431 mRNAs were changed after TCE exposure, of which 291 were up-regulated and 140 were down-regulated. Using qPCR, we validated six of the mRNA expression changed genes, viz., Jun, Cdkn1a, Rad51b, Uhrf1, Svil and Ihh. Six B6C3F1 male mice were oral administrated with either corn oil or TCE (dissolved in corn oil, 1000mg/kg b.w per day) for 5 days. The expression changes of mRNAs in TCE exposured mouse liver were screened by whole genome microarray expression profiling and were validated by qPCR.
2014-11-14 | E-GEOD-58819 | biostudies-arrayexpress
Project description:Trichloroethylene (TCE) is primarily used as an industrial degreasing agent and has been in use since the 1940s. TCE is released into the soil, surface, and groundwater. From an environmental and regulatory standpoint more than half of Superfund hazardous waste sites on the National Priority List are contaminated with TCE. Occupational exposure to TCE occurs primarily via inhalation, while environmental TCE exposure also occurs through ingestion of contaminated drinking water. Current literature links TCE exposure to various adverse health effects including cardiovascular toxicity. Current studies aiming to address developmental cardiovascular toxicity utilized rodent and avian models with the majority of studies using relatively higher parts per million (ppm; mg/L) doses. In this study to further investigate developmental cardiotoxicity of TCE, zebrafish embryos were treated with 0, 10, 100, or 500 parts per billion (ppb; μg/L) TCE during embryogenesis and/or through early larval stages. After the appropriate exposure period, angiogenesis, F-actin polymerization, and mitochondrial function were assessed. A significant dose response decrease in angiogenesis, F-actin polymerization, and mitochondrial function was observed. To further complement this data, a transcriptomic profile of zebrafish larvae was completed to identify gene alterations associated with the 10 ppb TCE exposure. Results from the transcriptomic data revealed that an embryonic TCE exposure caused significant changes in genes associated with cardiovascular disease, cancer, and organismal injury and abnormalities with a number of targets in the FAK signaling pathway. Overall, results from our study further support TCE as a developmental cardiovascular toxicant and continued priority for environmental regulation.
2016-02-01 | GSE72918 | GEO
Project description:Background/Aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.
2021-07-15 | GSE179961 | GEO
Project description:Exosomal or serum miRNA in liver disease
| PRJNA339060 | ENA
Project description:To examine changes, if any, in the expression of mRNAs in the liver tissue of mice, we have employed whole genome microarray expression profiling as a discovery platform to identify genes responsive to Trichloroethylene (TCE) treatment. In our results, the expression levels of 431 mRNAs were changed after TCE exposure, of which 291 were up-regulated and 140 were down-regulated. Using qPCR, we validated six of the mRNA expression changed genes, viz., Jun, Cdkn1a, Rad51b, Uhrf1, Svil and Ihh.
2014-11-14 | GSE58819 | GEO
Project description:The aim of this study was to identify and evaluate exosomal miRNAs in serum as early diagnostic markers for gastric cancer (GC). Methods: Using next-generation sequencing (NGS) and bioinformatics, we identified candidate serum exosomal miRNA markers for early detection of GC in patients. The candidates were further validated by qRT-PCR in 50 newly recruited early-stage GC patients and matched healthy individuals. Results: NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient. A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort after removal of log2 transformed read counts <5 and p >0.05. In the validation cohort, by comparing candidate exosomal miRNAs levels in early-stage GC patients and healthy individuals, higher levels of miR-92b-3p, let-7g-5p, miR-146b-5p and miR-9-5p were found to be significantly associated with GC. Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. In addition, serum levels of exosomal miR-92b-3p were significantly associated with low adhesion, let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration, and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC. Conclusions: Serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential noninvasive biomarkers for early diagnosis of GC. Further validation of these candidate exosomal miRNAs in larger experimental cohorts are required in order to confirm the diagnostic values.
2020-02-21 | GSE130654 | GEO