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Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice
The toxicological mechanisms of liver injury caused by most traditional Chinese medicine (TCM) remain largely unknown. Due to the unique features, exosomal microRNAs (miRNAs) are currently attracting major interests to provide further insights into toxicological mechanisms. Thus, taking Fructus Meli...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809479/ https://www.ncbi.nlm.nih.gov/pubmed/29434260 http://dx.doi.org/10.1038/s41598-018-21113-6 |
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author | Zheng, Jie Yu, Lingqi Chen, Wen Lu, Xiaoyan Fan, Xiaohui |
author_facet | Zheng, Jie Yu, Lingqi Chen, Wen Lu, Xiaoyan Fan, Xiaohui |
author_sort | Zheng, Jie |
collection | PubMed |
description | The toxicological mechanisms of liver injury caused by most traditional Chinese medicine (TCM) remain largely unknown. Due to the unique features, exosomal microRNAs (miRNAs) are currently attracting major interests to provide further insights into toxicological mechanisms. Thus, taking Fructus Meliae Toosendan as an example of hepatoxic TCM, this study aimed to elucidate its hepatotoxicity mechanisms through profiling miRNAs in circulating exosomes of Fructus Meliae Toosendan water extract (FMT)-exposed mice. Biological pathway analysis of the 64 differentially expressed exosomal miRNAs (DEMs) showed that hepatic dysfunction induced by FMT likely related to apoptosis, mitochondrial dysfunction, and cell cycle dysregulation. Integrated analysis of serum exosomal DEMs and hepatic differentially expressed mRNAs further enriched oxidative stress and apoptosis related pathways. In vitro validation studies for omics results suggested that FMT-induced DNA damage was mediated by generating intracellular reactive oxygen species, leading to cell apoptosis through p53-dependent mitochondrial damage and S-phase arrest. Nrf2-mediated antioxidant response was activated to protect liver cells. Moreover, serum exosomal miR-370-3p, the most down-regulated miRNA involving in these pathways, might be the momentous event in aggravating cytotoxic effect of FMT by elevating p21 and Cyclin E. In conclusion, circulating exosomal miRNAs profiling could contribute to deepen the understanding of TCM-induced hepatotoxicity. |
format | Online Article Text |
id | pubmed-5809479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58094792018-02-15 Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice Zheng, Jie Yu, Lingqi Chen, Wen Lu, Xiaoyan Fan, Xiaohui Sci Rep Article The toxicological mechanisms of liver injury caused by most traditional Chinese medicine (TCM) remain largely unknown. Due to the unique features, exosomal microRNAs (miRNAs) are currently attracting major interests to provide further insights into toxicological mechanisms. Thus, taking Fructus Meliae Toosendan as an example of hepatoxic TCM, this study aimed to elucidate its hepatotoxicity mechanisms through profiling miRNAs in circulating exosomes of Fructus Meliae Toosendan water extract (FMT)-exposed mice. Biological pathway analysis of the 64 differentially expressed exosomal miRNAs (DEMs) showed that hepatic dysfunction induced by FMT likely related to apoptosis, mitochondrial dysfunction, and cell cycle dysregulation. Integrated analysis of serum exosomal DEMs and hepatic differentially expressed mRNAs further enriched oxidative stress and apoptosis related pathways. In vitro validation studies for omics results suggested that FMT-induced DNA damage was mediated by generating intracellular reactive oxygen species, leading to cell apoptosis through p53-dependent mitochondrial damage and S-phase arrest. Nrf2-mediated antioxidant response was activated to protect liver cells. Moreover, serum exosomal miR-370-3p, the most down-regulated miRNA involving in these pathways, might be the momentous event in aggravating cytotoxic effect of FMT by elevating p21 and Cyclin E. In conclusion, circulating exosomal miRNAs profiling could contribute to deepen the understanding of TCM-induced hepatotoxicity. Nature Publishing Group UK 2018-02-12 /pmc/articles/PMC5809479/ /pubmed/29434260 http://dx.doi.org/10.1038/s41598-018-21113-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zheng, Jie Yu, Lingqi Chen, Wen Lu, Xiaoyan Fan, Xiaohui Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title | Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title_full | Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title_fullStr | Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title_full_unstemmed | Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title_short | Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice |
title_sort | circulating exosomal micrornas reveal the mechanism of fructus meliae toosendan-induced liver injury in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809479/ https://www.ncbi.nlm.nih.gov/pubmed/29434260 http://dx.doi.org/10.1038/s41598-018-21113-6 |
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