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暴露于环境双酚A会抑制HTR-8/SVneo细胞的迁移和侵袭。

Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion.

作者信息

Wei Pu, Ru Dongqing, Li Xiaoqian, Shi Dongyan, Zhang Mingshun, Xu Qing, Zhou Hong, Wen Shuang

机构信息

Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Department of Obstetrics, the Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, China.

出版信息

J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.

Abstract

Environmental pollutants, such as bisphenol A (BPA) have recently been implicated in the development of adverse birth outcomes. However, the underlying teratogenic mechanisms remain unclear. We investigated the effects of BPA on the migration and invasion of human primary extravillous trophoblast HTR-8/SVneo cells. Our results indicated that BPA reduced cell migration and invasion. Moreover, it altered the ratio of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) by downregulating MMP-2 and MMP-9, and upregulating TIMP-1 and TIMP-2. Furthermore, BPA suppressed integrin β1, integrin α5, and vimentin. Interestingly, BPA-induced invasion was partially restored by G15, a membrane G-protein-coupled estrogen receptor 30 antagonist. We further revealed that 42 proteins were differentially expressed by mass spectrometry analysis, which could be divided into three categories based on gene ontology including biological process, cellular component, and molecular function. These results suggest that BPA reduces HTR-8/SVneo cell migration and invasion by downregulating MMP-2 and MMP-9, up-regulating TIMP-1 and TIMP-2, and suppressing adhesion molecules.

摘要

环境污染物,如双酚A(BPA),最近被认为与不良出生结局的发生有关。然而,其潜在的致畸机制仍不清楚。我们研究了BPA对人原代绒毛外滋养层细胞HTR-8/SVneo迁移和侵袭的影响。我们的结果表明,BPA降低了细胞的迁移和侵袭能力。此外,它通过下调基质金属蛋白酶(MMPs)-2和MMP-9,上调MMPs组织抑制剂(TIMPs)-1和TIMP-2,改变了MMPs与TIMPs的比例。此外,BPA抑制整合素β1、整合素α5和波形蛋白。有趣的是,膜G蛋白偶联雌激素受体30拮抗剂G15部分恢复了BPA诱导的侵袭。我们进一步通过质谱分析揭示了42种差异表达的蛋白质,根据基因本体论可分为生物过程、细胞成分和分子功能三类。这些结果表明,BPA通过下调MMP-2和MMP-9、上调TIMP-1和TIMP-2以及抑制黏附分子来降低HTR-8/SVneo细胞的迁移和侵袭能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b25e/7540237/4c0240b216d3/jbr-34-5-369-1.jpg

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