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线虫秀丽隐杆线虫中 DBL-1/TGF-β 信号介导的神经元-肠通讯对纳米聚苯乙烯的反应。

Response of DBL-1/TGF-β signaling-mediated neuron-intestine communication to nanopolystyrene in nematode Caenorhabditis elegans.

机构信息

Medical School, Southeast University, Nanjing 210009, China.

Medical School, Southeast University, Nanjing 210009, China; Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen 518122, China.

出版信息

Sci Total Environ. 2020 Nov 25;745:141047. doi: 10.1016/j.scitotenv.2020.141047. Epub 2020 Jul 27.

DOI:10.1016/j.scitotenv.2020.141047
PMID:32758726
Abstract

TGF-β signaling pathway is important for the regulation of stress response in organisms. We here used Caenorhabditis elegans to determine the function of DBL-1/TGF-β signaling pathway in the control of response to nanopolystyrene (100 nm). In DBL-1/TGF-β signaling pathway, exposure to 1-1000 μg/L nanopolystyrene significantly increased the expressions of dbl-1 encoding a TGF-β ligand, sma-6 encoding a TGF-β receptor, sma-4 encoding a Co-Smad, and two genes (mab-31 and sma-9) encoding transcriptional factors. DBL-1 acted in the neurons to control the response to nanopolystyrene. In the neurons, the expression and the function of DBL-1 were under the control of two signaling cascades (SMOC-1-ZAG-1 and SMOC-1-ADT-2). TGF-β receptor SMA-6 acted in the intestine to control the response to nanopolystyrene. The downstream Co-Smad/SMA-4 and two transcriptional factors (MAB-31 and SMA-9) of SMA-6 in the intestine were further identified to be required for the control of response to nanopolystyrene. In nanopolystyrene exposed nematodes, intestinal MAB-31 activated the mitochondrial Mn-SOD/SOD-3 by modulating DAF-16 activity, and intestinal SMA-9 activated the mitochondrial unfolded protein response by affecting ELT-2 activity. Therefore, the DBL-1/TGF-β signaling pathway mediated an important neuron-intestine communication in nanopolystyrene exposed nematodes.

摘要

TGF-β 信号通路对于生物的应激反应调控非常重要。在这里,我们利用秀丽隐杆线虫来确定 DBL-1/TGF-β 信号通路在控制其对纳米聚苯乙烯(100nm)响应中的作用。在 DBL-1/TGF-β 信号通路中,暴露于 1-1000μg/L 的纳米聚苯乙烯显著增加了 TGF-β 配体编码基因 dbl-1、TGF-β 受体编码基因 sma-6、Co-Smad 编码基因 sma-4 以及两个转录因子编码基因(mab-31 和 sma-9)的表达。DBL-1 在神经元中起作用,以控制其对纳米聚苯乙烯的响应。在神经元中,DBL-1 的表达和功能受两条信号级联(SMOC-1-ZAG-1 和 SMOC-1-ADT-2)的控制。TGF-β 受体 SMA-6 在肠道中起作用,以控制其对纳米聚苯乙烯的响应。进一步鉴定出 SMA-6 在肠道中的下游 Co-Smad/SMA-4 和两个转录因子(MAB-31 和 SMA-9)对于控制对纳米聚苯乙烯的响应是必需的。在暴露于纳米聚苯乙烯的线虫中,肠道中的 MAB-31 通过调节 DAF-16 活性激活线粒体 Mn-SOD/SOD-3,而肠道中的 SMA-9 通过影响 ELT-2 活性激活线粒体未折叠蛋白反应。因此,DBL-1/TGF-β 信号通路介导了暴露于纳米聚苯乙烯的线虫中重要的神经元-肠道通讯。

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