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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146710 | GEO | 2021/03/05

REPOSITORIES: GEO

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

Project description: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.

2021-03-05 | GSE146551 | GEO

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

Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis

| PRJNA611721 | ENA

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

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

| PRJNA611710 | ENA

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

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

| PRJNA611724 | ENA

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

Lung response to multi-walled carbon nanotube exposure in rats.

Project description:The projected increase in the production and use of nanomaterials is expected to result in a corresponding increase in human exposure, potentially resulting in significant morbidity and mortality. Currently, the lung toxicity of multi-walled carbon nanotubes (MWCNT), a prototype nanomaterial, was investigated in a rat model. The rats were exposed by whole-body inhalation to air (controls) or MWCNT (6 hours/day, 3 days) to result in cumulative doses of 180, 90, 45, 22.5, or 11.25 mg/m3. Lung toxicity and gene expression profiles were determined in the lungs of the control and MWCNT exposed rats one day following termination of the exposures. Moderate lung histological changes, indicative of toxicity, were detected in rats exposed to MWCNT at doses > 45 mg/m3. Changes in toxicity parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts of phagocytes, and cytokine levels were detected in the bronchoalveolar lavage of rats exposed to > 22.5 mg/m3 MWCNT, compared with the air controls. Lung gene expression profiling detected differences in transcript levels (fold change >1.5 and FDR p<0.05) of several genes in the rats exposed to >22.5 mg/m3 MWCNT, compared with the controls. The changes in lung toxicity and gene expression profiles exhibited a dose-response to the MWCNT administered in the rats.

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