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五溴苯酚通过网格蛋白介导的内吞作用加速 II 型 TGF-β 受体的降解来抑制 TGF-β 信号通路。

Pentabromophenol suppresses TGF-β signaling by accelerating degradation of type II TGF-β receptors via caveolae-mediated endocytosis.

机构信息

Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.

Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan, ROC.

出版信息

Sci Rep. 2017 Feb 23;7:43206. doi: 10.1038/srep43206.

Abstract

Pentabromophenol (PBP), a brominated flame retardant (BFR), is widely used in various consumer products. BFRs exert adverse health effects such as neurotoxic and endocrine-disrupting effects. In this study, we found that PBP suppressed TGF-β response by accelerating the turnover rate of TGF-β receptors. PBP suppressed TGF-β-mediated cell migration, PAI-1 promoter-driven reporter gene activation, and Smad2/3 phosphorylation in various cell types. Furthermore, PBP abolished TGF-β-mediated repression of E-cadherin expression, in addition to the induction of vimentin expression and N-cadherin and fibronectin upregulation, thus blocking TGF-β-induced epithelial-mesenchymal transition in A549 and NMuMG cells. However, this inhibition was not observed with other congeners such as tribromophenol and triiodophenol. TGF-β superfamily members play key roles in regulating various biological processes including cell proliferation and migration as well as cancer development and progression. The results of this in vitro study provide a basis for studies on the detailed relationship between PBP and modulation of TGF-β signalling. Because PBP is similar to other BFRs such as polybrominated diphenyl ethers (PBDEs), additional laboratory and mechanistic studies should be performed to examine BFRs as potential risk factors for tumorigenesis and other TGF-β-related diseases.

摘要

五溴苯酚(PBP)是一种溴化阻燃剂(BFR),广泛应用于各种消费品中。BFR 会对健康产生不良影响,如神经毒性和内分泌干扰效应。在这项研究中,我们发现 PBP 通过加速 TGF-β 受体的周转率来抑制 TGF-β 反应。PBP 抑制了 TGF-β 介导的细胞迁移、PAI-1 启动子驱动的报告基因激活以及各种细胞类型中的 Smad2/3 磷酸化。此外,PBP 还消除了 TGF-β 介导的 E-钙粘蛋白表达抑制,以及诱导波形蛋白表达和 N-钙粘蛋白和纤维连接蛋白上调,从而阻断了 TGF-β 在 A549 和 NMuMG 细胞中的上皮-间充质转化。然而,这种抑制作用在其他同系物如三溴苯酚和三碘苯酚中并未观察到。TGF-β 超家族成员在调节细胞增殖和迁移以及癌症发生和发展等各种生物学过程中发挥着关键作用。这项体外研究的结果为研究 PBP 与 TGF-β 信号调节之间的详细关系提供了依据。由于 PBP 与其他 BFR 如多溴联苯醚(PBDEs)相似,因此应该进行更多的实验室和机制研究,以检查 BFR 作为肿瘤发生和其他 TGF-β 相关疾病的潜在风险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4985/5322341/d2183539aa98/srep43206-f1.jpg

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