Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [methylation]

ABSTRACT: Toxicogenomics approaches are increasingly applied to gain mechanistic insight into the toxicity of engineered nanomaterials (ENMs). These emerging technologies have been shown to aid the translation of in vitro experimentation into relevant information on real-life exposures. Furthermore, integrating multiple layers of molecular alteration can improve the systemic understanding of the toxicological insult. While evidence of the immunotoxic effects of several ENMs is arising, the mechanisms are less characterized, and the dynamics of the molecular adaptation of the immune cells are still largely unknown. Here, we carried out a multi-omics approach characterizing the dynamic dose-dependent (DDD) molecular alterations in a model of human macrophages. THP-1 macrophages were exposed to increasing concentrations of rigid multiwalled carbon nanotubes (rCNTs) and the genome-wide alterations in the transcriptome and gene promoter methylation were assessed at three consecutive time points. The results suggest dynamic patterns of molecular alterations with a rapid response in the gene expression and contribution of DNA methylation in the long-term adaptation. Moreover, our analytical approach is able to highlight patterns of molecular alteration in vitro that recapitulate several elements of pathogenesis of pulmonary fibrosis, a known long-term effect of rCNTs exposure in vivo.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146551 | GEO | 2021/03/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]

Project description:Multi-omics approach to characterize the dynamic dose-dependent (DDD) molecular alterations in a model of human macrophages was used to highlight key-genes altered due to rCNT exposure. Results emphasize short and long term changes in gene regulation, that further suggest fibrotic responses, previously reported in in vivo animal model.

2021-03-05 | GSE146708 | GEO

Multi-parametric profiling of a large panel of engineered nanomaterials (ENM) points to surface chemistry as a key determinant of nanomaterial effects

Project description:Monocytic, cancer derived THP-1 cells were exposed to 31 different engineered nanomaterials (ENMs) with different core chemistries and surface modifications for 24 hours.

2020-12-01 | GSE148705 | GEO

Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

Project description:Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to perform genome-wide mRNA profiling in mice blood to identify non-invasive blood based biomarkers for medical and occupational surveillance. The pathological results in this 1-year MWCNT post-exposure study was previously published in Snyder-Talkington et al. J Toxicol Environ Health A. 2016;79(8):352-66. doi: 10.1080/15287394.2016.1159635. Epub 2016 Apr 19. PMID: 27092743

2019-07-26 | GSE126959 | GEO

Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test

Project description:Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.

2023-07-17 | GSE234151 | GEO

Toxicity mechanisms of ZnO UV-filters used in sunscreens toward the model cyanobacteria Synechococcus elongatus PCC7942

Project description:Zinc oxide (ZnO) nanoparticles are commonly used in sunscreens for their UV-filtering properties. Their growing use can lead to their release into ecosystems, raising question about their toxicity. Effects of these engineered nanomaterials (ENMs) on cyanobacteria, which are important primary producers involved in many biogeochemical cycles, are unknown. In this study, we investigated by several complementary approaches the toxicological effects of two marketed ZnO-ENMs (coated and uncoated) on the model cyanobacteria Synechococcus elongatus PCC 7942. It was shown that despite the rapid adsorption of ENMs on cell surface, toxicity is mainly due to labile Zn released by ENMs. Zn dissipates cell membrane potential necessary for both photosynthesis and respiration, and induces oxidative stress leading to lipid peroxidation and DNA damages. It leads to global downregulation of photosystems, oxidative phosphorylation, and transcription/translation machineries. This also translates into significant decrease of intracellular ATP content and cell growth inhibition. However, there is no major loss of pigments and even rather an increase in exposed cells compared to controls. A proposed way to reduce the environmental impact of Zn would be the improvement of the coating stability to prevent solubility of ZnO-ENMs.

2019-06-05 | GSE102914 | GEO

Apolipoprotein E is associated with dense deposits in dense deposit disease

Project description:C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway (AP) of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both C3GN and DDD are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy, DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known.We performed laser microdissection of glomeruli followed by mass spectrometry in 12 known cases of DDD and C3GN each to determine the proteomic profile and differences between C3GN and DDD.

2024-10-22 | PXD045319 | Pride

Multi-walled carbon nanotube-induced gene expression in vitro

Project description:There is a current interest in reducing the in vivo toxicity testing of nanomaterials in animals by increasing toxicity testing using in vitro cellular assays; however, toxicological results are seldom concordant between in vivo and in vitro models. This study compared global multi-walled carbon nanotube (MWCNT)-induced gene expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with gene expression from mouse lungs exposed to MWCNT. Using a cutoff of 10% false discovery rate and 1.5 fold change, we determined that there were more concordant genes (gene expression both up- or downregulated in vivo and in vitro) expressed in both cell types in coculture than in monoculture. When reduced to only those genes involved in inflammation and fibrosis, known outcomes of in vivo MWCNT exposure, there were more disease-related concordant genes expressed in coculture than monoculture. Additionally, different cellular signaling pathways are activated in response to MWCNT dependent upon culturing conditions. As coculture gene expression better correlated with in vivo gene expression, we suggest that cellular cocultures may offer enhanced in vitro models for nanoparticle risk assessment and the reduction of in vivo toxicological testing.

2019-04-12 | GSE129640 | GEO

Proteome changes in monocytic THP-1 cells induced by 31 engineered nanomaterials

Project description:Here, we investigated a panel of 31 engineered nanomaterials (ENMs) with different core chemistries and surface modifications using conventional cytotoxicity assays coupled with omics-based approaches. Proteomics analysis were conducted in order to monitor changes in cells proteome exposed to ENMs. In this standard approach, cells are exposed to various types and amounts of ENMs and proteins are extracted after a given exposure period. For controls, no ENM are applied but the incubation and extraction of proteins is done the same way. Proteome changes are monitored using high-resolution Fourier transform mass spectrometry (Orbitraps) as well as in-house developed label-free software. Similar approaches have been used for quantitative analysis of posttranslational modifications. Proteomics analyses following low-dose exposure of THP-1 cells suggested a non-specific stress response to ENMs while microarray-based profiling revealed significant changes in gene expression as a function of both surface functionalization and core chemistry of the ENMs. Pathway analysis revealed that the most biologically active ENMs displaying cationic surfaces downregulated DNA replication/cell cycle responses and upregulated inflammatory responses. This study shows that surface chemistry is a key determinant of nanomaterial effects on immune cells.

2021-09-09 | PXD019267 | Pride

Carbon nanotubes, but not graphene oxide, trigger chemokine production in primary human macrophages via MyD88 dependent NF-kB Pathway

Project description:The growing medical application of engineered nanomaterials (ENMs) necessitates better understanding of their molecular toxicity mechanisms governing immune effects. In the present study, a comprehensive mechanistic in vitro assessment of two carbon-based ENMs, single-walled carbon nanotubes (SWCNTs) and graphene oxide (GO), was performed using primary human monocyte-derived macrophages (HMDM) as a model. HMDM were exposed to SWCNTs and GO at concentrations 10–100 µg/ml for 24 h. Toxicity, reactive oxygen species (ROS) production and uptake of ENM by cells was measured. The changes in gene expression profile of HMDM in response to SWCNTs and GO were studied and the key stress response pathways identified. The transcriptomics and pathway enrichment analysis findings were verified by multiplex immunoassay and functional assays.

2017-09-30 | GSE83516 | GEO

Methylation dataset of multi regional colorectal carcinoma.

Project description:Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of eight colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients’ ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

2016-10-18 | GSE88821 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data