Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study.
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE126959
PROVIDER: PRJNA448940 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
Project description:Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.
| PRJNA523853 | ENA
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 examine the effects of 1, 10, 40, or 80 µg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-µg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 µg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.
2018-04-06 | GSE112780 | GEO
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
Project description:Mice were aspirated with multiwalled carbon nanotubes in four doses ranging from 10 µg to 80 µg, plus control, and sacrificed after 1, 7, 28, and 56 days. RNA was extracted from the lungs and expression profilling by microarray was performed. This is a reference design two-color experiment. Each array was hybridized with RNA extracted from mouse lung labeled with Cy3, and universal reference RNA labeled with Cy5. Five different doses (0, 10ug, 20ug, 40ug, and 80ug) of multiwalled carbon nanotube aspiration were used and mice were sacrificed after 1, 7, 28, and 56 days. Eight replicates were used at each time/dose condition for a total of 160 arrays.
2012-06-25 | E-GEOD-29042 | biostudies-arrayexpress
Project description:Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test
| PRJNA980209 | ENA
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 examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.
| S-EPMC4899319 | biostudies-literature
Project description:Introduction. Factors contributing to kidney transplant fibrosis remain incompletely understood—particularly in the absence of acute complications. Methods. Baseline and one-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative RT-PCR (qRT-PCR) analyses in order to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n = 7) and those that had developed subclinical interstitial fibrosis (n = 8) at 1 year. Results. Compared to the paired baseline specimens, expression levels of 3578 probesets were found altered in all the one-year biopsies studied. A large proportion of the upregulated genes in this transplant-associated profile were functionally linked with inflammation, immunity or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon and TLR) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile were also predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles. Conclusions. Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate post-transplant period. Subclinical development of interstitial fibrosis during the first post-transplant year is associated with additional upregulation of inflammation-related genes. Keywords: time course, comparative expression We analyzed gene expression from a group of 15 renal transplant patients. All patients had histologically normal time zero biopsy but while 7 remained histologically normal (TxNorm), 8 developed subclinical interstitial fibrosis (GIF/TA) by 1 year. Patient groups were carefully selected to include patients on the same immunosuppresion therapy, transplant type, biopsy histology and absence of overt post-transplant complications (acute rejection, BK, etc). This dataset is part of the TransQST collection.
2007-03-30 | E-GEOD-7392 | biostudies-arrayexpress
Project description:Functionalized carbon nanotube toxicity in Arabidopsis leaves
| PRJNA722743 | ENA
Project description:Introduction. Factors contributing to kidney transplant fibrosis remain incompletely understood—particularly in the absence of acute complications. Methods. Baseline and one-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative RT-PCR (qRT-PCR) analyses in order to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n = 7) and those that had developed subclinical interstitial fibrosis (n = 8) at 1 year. Results. Compared to the paired baseline specimens, expression levels of 3578 probesets were found altered in all the one-year biopsies studied. A large proportion of the upregulated genes in this transplant-associated profile were functionally linked with inflammation, immunity or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon and TLR) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile were also predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles. Conclusions. Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate post-transplant period. Subclinical development of interstitial fibrosis during the first post-transplant year is associated with additional upregulation of inflammation-related genes. Keywords: time course, comparative expression
2007-03-30 | GSE7392 | GEO