دورية أكاديمية
Fluoride exposure induces lysosomal dysfunction unveiled by an integrated transcriptomic and metabolomic study in bone marrow mesenchymal stem cells
| العنوان: | Fluoride exposure induces lysosomal dysfunction unveiled by an integrated transcriptomic and metabolomic study in bone marrow mesenchymal stem cells |
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| المؤلفون: | Hui Wang, Lu Yang, Peng Gao, Ping Deng, Yang Yue, Li Tian, Jia Xie, Mengyan Chen, Yan Luo, Yidan Liang, Weijia Qing, Zhou Zhou, Huifeng Pi, Zhengping Yu |
| المصدر: | Ecotoxicology and Environmental Safety, Vol 239, Iss , Pp 113672- (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
| مصطلحات موضوعية: | Fluoride, Bone marrow mesenchymal stem cells, Lysosome, Transcriptomic, Metabolomic, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| الوصف: | Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. In this study, BMSCs were exposed to fluoride at 1, 2, and 4 mM for 24 h, and fluoride significantly inhibited cell viability at 2 and 4 mM. A multiomics analysis combining transcriptomics with metabolomics was employed to detect alterations in genes and metabolites in BMSCs treated with 2 mM fluoride. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of transcriptomics profiles identified “lysosomes” as the top enriched pathway, which was severely damaged by fluoride exposure. Lysosomal damage was indicated by decreases in the expression of lysosomal associated membrane protein 2 (LAMP 2) and cathepsin B (CTSB) as well as an increase in pH. Upregulation of the lysosome-related genes Atp6v0b and Gla was observed, which may be attributed to a compensatory lysosomal biogenesis transcriptional response. Interestingly, inhibition of glutathione metabolism was observed in fluoride-treated BMSCs at the metabolomic level. Moreover, an integrative analysis between altered genes, metabolites and lysosome signaling pathways was conducted. Palmitic acid, prostaglandin C2, and prostaglandin B2 metabolites were positively associated with Atp6v0b, a lysosome-related gene. Overall, our results provide novel insights into the mechanism responsible for fluoride-induced bone toxicity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0147-6513 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S0147651322005127Test; https://doaj.org/toc/0147-6513Test |
| DOI: | 10.1016/j.ecoenv.2022.113672 |
| الوصول الحر: | https://doaj.org/article/9e822bbff96b44ee912b26d7b40ad320Test |
| رقم الانضمام: | edsdoj.9e822bbff96b44ee912b26d7b40ad320 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 01476513 |
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| DOI: | 10.1016/j.ecoenv.2022.113672 |