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JAK/STAT and TGF-ß activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017), Kim, H, Jeong, J, Chatterjee, N, Roca, C P, Yoon, D, Kim, S, Kim, Y & Choi, J 2017, ' JAK/STAT and TGF-beta activation as potential adverse outcome pathway of TiO(2)NPs phototoxicity in &ITCaenorhabditis elegans &IT ', Scientific Reports, vol. 7, 17833 . https://doi.org/10.1038/s41598-017-17495-8
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Titanium dioxide nanoparticles (TiO2NPs) are widely used nanoparticles, whose catalytic activity is mainly due to photoactivation. In this study, the toxicity of TiO2NPs was investigated on the nematode Caenorhabditis elegans, with and without UV activation. Comparative analyses across the four treatments revealed that UV-activated TiO2NPs led to significant reproductive toxicity through oxidative stress. To understand the underlying molecular mechanism, transcriptomics and metabolomics analyses were conducted, followed by whole-genome network-based pathway analyses. Differential expression analysis from microarray data revealed only 4 DEGs by exposure to TiO2NPs alone, compared to 3,625 and 3,286 DEGs by UV alone and UV-activated TiO2NPs, respectively. Pathway analyses suggested the possible involvement of the JAK/STAT and TGF-ß pathways in the phototoxicity of TiO2NPs, which correlated with the observation of increased gene expression of those pathways. Comparative analysis of C. elegans response across UV activation and TiO2NPs exposure was performed using loss-of-function mutants of genes in these pathways. Results indicated that the JAK/STAT pathway was specific to TiO2NPs, whereas the TGF-ß pathway was specific to UV. Interestingly, crosstalk between these pathways was confirmed by further mutant analysis. We consider that these findings will contribute to understand the molecular mechanisms of toxicity of TiO2NPs in the natural environment.
- Subjects :
- MECHANISM
0301 basic medicine
Mutant
lcsh:Medicine
SYSTEMS TOXICOLOGY APPROACH
METABOLOMICS
TOXICITY
stat
Transcriptome
03 medical and health sciences
Gene expression
lcsh:Science
Caenorhabditis elegans
GENE-EXPRESSION
Multidisciplinary
biology
Chemistry
Microarray analysis techniques
TITANIUM-DIOXIDE NANOPARTICLES
lcsh:R
technology, industry, and agriculture
JAK-STAT signaling pathway
ROS
biology.organism_classification
Cell biology
REPRODUCTION
030104 developmental biology
TIO2 NANOPARTICLES
lcsh:Q
CAENORHABDITIS-ELEGANS
Phototoxicity
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....1510874a63180fafd99b56d25c1c850e
- Full Text :
- https://doi.org/10.1038/s41598-017-17495-8