Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity

Du, Guizhen; Yu, Mingming; Wang, Lingling; Hu, Wu; Lee, Song; Lu, Chuncheng; Wang, Xinru

doi:10.1155/2018/8608327

Cited by 13 publications

(7 citation statements)

References 31 publications

(37 reference statements)

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“…Their results showed that in the 5735 CpG dinucleotides, 2960 were related to suppressed gene expression, which showed no significant difference with the number of CpGs (2775) whose methylation levels were positively associated with gene expression. Table summarized the relationship between DNA methylation and gene expression . These results indicated that DNA methylation functions as a bidirectional modulator in regulating gene expression, depending on the location of CpG sites, DNA methylation detection method, disease context and specific gene.…”

Section: Discussionmentioning

confidence: 97%

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Yang

Wang

et al. 2019

J of Cellular Biochemistry

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Cardiac development is a peculiar process involving coordinated cellular differentiation, migration, proliferation, and apoptosis. DNA methylation plays a key role in genomic stability, tissue‐specific gene expression, cell proliferation, and apoptosis. Hypomethylation in the global genome has been reported in cardiovascular diseases. However, little is known about the impact and specific mechanism of global hypomethylation on cardiomyocytes. In the present study, we explored the impact of DNA methyltransferase inhibitors 5‐azacytidine on cardiac development. In vivo experiment showed that hypomethylation of zebrafish embryos with 5‐azacytidine exposure significantly reduced survival, induced malformations, and delayed general development process. Furthermore, zebrafish embryos injected with 5‐azacytidine developed pericardial edema, ventricular volume reduction, looping deformity, and reduction in heart rate and ventricular shortening fraction. Cardiomyocytes treated with 5‐azacytidine in vitro decreased proliferation and induced apoptosis in a concentration‐dependent manner. Furthermore, 5‐azacytidine treatment in cardiomyocytes resulted in 20 downregulated genes expression and two upregulated genes expression in 45 candidate genes, which indicated that DNA methylation functions as a bidirectional modulator in regulating gene expression. In conclusion, these results show the regulative effects of the epigenetic modifier 5‐azacytidine in cardiac development of zebrafish embryos in vivo and cardiomyocyte proliferation and apoptosis and the homeostasis of gene expression in vitro, which offer a novel understanding of aberrant DNA methylation in the etiology of cardiovascular disease.

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Section: Discussionmentioning

confidence: 97%

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Yang

Wang

et al. 2019

J of Cellular Biochemistry

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“…The formation of dental arch depends on the coordinated regulation of a variety of signaling molecules and location signals, which jointly regulate the development process of cell division rate, trend and direction of cell migration, cell differentiation and apoptosis. In the above process, a series of genes and signaling pathways play an important role in regulation, including Sonic hedgehog (Shh) pathway [ 5 ], Wingless-related integration (Wnt) pathway [ 6 ], fibroblast growth factors (FGF) pathway [ 7 ], Transforming growth factor-beta (TGF-β) [ 8 ] pathway and bone morphogenesis proteins (BMPs) family [ 9 – 11 ]. These signaling molecules bind to corresponding receptors and regulate the expression of specific genes.…”

Section: Introductionmentioning

confidence: 99%

A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development

Shi

Zhou

et al. 2021

Cell Biosci

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Background Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. Result To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via Transforming growth factor-β, Tumor necrosis factor (TNF) and Interleukin-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that Colony Stimulating Factor 1 secreted from pericyte and TNF Superfamily Member 11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. Conclusions We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology.

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“…In this study, exposure to TCS (1 µM) inhibited the differentiation of hESCs into cardiomyocytes and their spontaneous beating. This inhibition occurred through the interference of triclosan with the gene expression (of ACTC1, GATA4, and TNNT2) and with excessive methylations in the DNA [ 81 ].…”

Section: Effects On the Cardiovascular Systemmentioning

confidence: 99%

Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels

Marques

Mariana

Cairrão

2022

IJMS

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Hygiene is essential to avoid diseases, and this is thanks to daily cleaning and disinfection habits. Currently, there are numerous commercial products containing antimicrobial agents, and although they are efficient in disinfecting, it is still not known the effect of the constant use of these products on human health. In fact, a massive use of disinfectants has been observed due to COVID-19, but the possible adverse effects are not yet known. Triclosan is one of the antimicrobial agents used in cosmetic products, toothpaste, and disinfectants. This compound is an endocrine disruptor, which means it can interfere with hormonal function, with its estrogenic and androgenic activity having already been stated. Even if the use of triclosan is well-regulated, with the maximum allowed concentration in the European Union of 0.3% (m/m), its effects on human health are still uncertain. Studies in animals and humans suggest the possibility of harmful health outcomes, particularly for the reproductive system, and in a less extent for the cardiovascular and thyroid functions. Thus, the purpose of this review was to analyse the possible implications of the massive use of triclosan, mainly on the reproductive and cardiovascular systems and on the thyroid function, both in animals and humans.

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Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity

Cited by 13 publications

References 31 publications

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

Impact of DNA methyltransferase inhibitor 5‐azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro

A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development

Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels

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