Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models
文献类型：期刊论文
| 作者 | Zhu, Min; Niu, Yue; Li, Yuanyuan; Dong, Mengqi; Li, Jinbo ; Zeng, Ran; Qin, Zhanfen
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| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
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| 出版日期 | 2020-06-15 |
| 卷号 | 33期号:6页码:1418-1427 |
| ISSN号 | 0893-228X |
| 英文摘要 | Tetrabromobisphenol A (TBBPA) was recently reported to upregulate Notch target gene expression in embryonic stem cells differentiating to neurons in vitro, implying activation on Notch signaling, a crucial signaling involved in multiple organ development and homeostasis.The present study aimed to determine whether TBBPA at low concentrations can disrupt Notch signaling in the intestine and subsequently its development using in vitro and in vivo models, given TBBPA uptake mainly via the intestine. In rat intestinal epithelium cells (IEC-6), an in vitro model for intestinal development and homeostasis, we found 5-500 nM TBBPA upregulated Notch-related gene expression and stimulated cell proliferation as well as the growth of microvilli in a linear concentration-dependent manner. When Notch inhibitor DAPT had no obvious effects on all end points, DAPT significantly antagonized all changes caused by TBBPA, indicating that TBBPA activated Notch signaling in IEC-6 cells and subsequently stimulated cell proliferation and differentiation. Then we employed Xenopus laevis, an ideal model species for intestinal development with the strong similarities to mammals, to further confirm the action of TBBPA in vivo. Expectedly, we observed the stimulatory effects of TBBPA on Notch signaling and cell proliferation and differentiation in X. laevis intestines, which agrees with the results in vitro. Antagonistic actions of Notch inhibitor DBZ on TBBPA-caused intestinal changes show that TBBPA affected intestinal development via disrupting Notch signaling. Interestingly, TBBPA stimulated cell differentiation into secretory cells, which is generally believed to be regulated by Wnt signaling, suggesting disruption of Wnt signaling besides Notch signaling. All the results for the first time demonstrate that TBBPA at low concentrations, including environmentally relevant concentrations, disrupt Notch signaling and subsequently affect intestinal development by altering cell proliferation and differentiation in vertebrates. Our study highlights the intestine as a new target of TBBPA and broaden our understanding of developmental toxicity of TBBPA. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/44726]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Zhu, Min,Niu, Yue,Li, Yuanyuan,et al. Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2020,33(6):1418-1427. |
| APA | Zhu, Min.,Niu, Yue.,Li, Yuanyuan.,Dong, Mengqi.,Li, Jinbo.,...&Qin, Zhanfen.(2020).Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models.CHEMICAL RESEARCH IN TOXICOLOGY,33(6),1418-1427. |
| MLA | Zhu, Min,et al."Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models".CHEMICAL RESEARCH IN TOXICOLOGY 33.6(2020):1418-1427. |
入库方式： OAI收割
来源：生态环境研究中心
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