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The Differential Effect of Carbon Dots on Gene Expression and DNA Methylation of Human Embryonic Lung Fibroblasts as a Function of Surface Charge and Dose
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SYSNO ASEP 0532291 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Differential Effect of Carbon Dots on Gene Expression and DNA Methylation of Human Embryonic Lung Fibroblasts as a Function of Surface Charge and Dose Author(s) Šíma, Michal (UEM-P) RID, ORCID
Vrbová, Kristýna (UEM-P)
Závodná, Táňa (UEM-P)
Hoňková, Kateřina (UEM-P)
Chvojková, Irena (UEM-P)
Ambrož, Antonín (UEM-P)
Kléma, J. (CZ)
Rössnerová, Andrea (UEM-P) RID
Poláková, K. (CZ)
Malina, T. (CZ)
Belza, J. (CZ)
Topinka, Jan (UEM-P) RID, ORCID
Rössner ml., Pavel (UEM-P) RID, ORCIDArticle number 4763 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 21, č. 13 (2020)Number of pages 23 s. Publication form Print - P Language eng - English Country CH - Switzerland Keywords carbon dots ; surface charge ; human lung fibroblasts Subject RIV EB - Genetics ; Molecular Biology OECD category Genetics and heredity (medical genetics to be 3) R&D Projects LO1508 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015073 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 000550217600001 EID SCOPUS 85087454236 DOI 10.3390/ijms21134763 Annotation This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 mu g/mL (for positive charged CD, pCD) or 10 and 100 mu g/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2021 Electronic address https://www.mdpi.com/1422-0067/21/13/4763
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