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低剂量双酚 A 通过激活 LUMAN 介导的未折叠蛋白反应损害小鼠蜕膜基质细胞的功能。

Low-dose bisphenol A impairs the function of mouse decidual stromal cells by activating LUMAN-mediated unfolded protein response.

机构信息

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.

出版信息

Food Chem Toxicol. 2021 Jul;153:112242. doi: 10.1016/j.fct.2021.112242. Epub 2021 Apr 27.

DOI:10.1016/j.fct.2021.112242
PMID:33930482
Abstract

The nonsteroidal estrogenic compound bisphenol A (BPA) is widely present in several industrial and medical products including plastic food containers and sealants in dentistry. There are growing concerns on the toxic effects of this compounds since BPA is known to have reproductive toxicity. This study evaluated the effects of low-dose BPA exposure on decidual stromal cells (DSCs) of mice. The results showed that although 10 nM of BPA have no significant effect on the cell viability, it alters the expression of decidualization-related genes including Prl8a2, Prl3c1, Ptgs2, and Mmp2. Moreover, we found that low-dose BPA exposure induces UPR response in DSCs. However, the expression of the three major UPR receptors (Perk, Ire 1, and Xbp1) did not change significantly. Interestingly, the expression of Luman, a novel receptor of UPR, was significantly upregulated in a dose-dependent manner. Lentivirus containing shLuman sequence was used to generate stable Luman silencing DSCs. It's showed that Luman knockdown could affect the expression of decidualization-related genes in decidual cells after BPA treatment. In summary, these results suggest that Luman plays a key role in low dose BPA-induced decidual toxicity of DSCs in mouse.

摘要

非甾体雌激素化合物双酚 A(BPA)广泛存在于多种工业和医疗产品中,包括塑料食品容器和牙科用密封剂。由于 BPA 具有生殖毒性,人们对这种化合物的毒性作用越来越关注。本研究评估了低剂量 BPA 暴露对小鼠蜕膜基质细胞(DSC)的影响。结果表明,尽管 10 nM 的 BPA 对细胞活力没有显著影响,但它改变了蜕膜化相关基因的表达,包括 Prl8a2、Prl3c1、Ptgs2 和 Mmp2。此外,我们发现低剂量 BPA 暴露诱导 DSCs 发生未折叠蛋白反应(UPR)。然而,三种主要 UPR 受体(Perk、Ire 1 和 Xbp1)的表达没有明显变化。有趣的是,UPR 的一种新型受体 Luman 的表达呈剂量依赖性显著上调。含有 shLuman 序列的慢病毒用于生成稳定沉默 Luman 的 DSCs。结果表明,Luman 敲低可影响 BPA 处理后蜕膜细胞中蜕膜化相关基因的表达。综上所述,这些结果表明 Luman 在低剂量 BPA 诱导的小鼠 DSCs 蜕膜毒性中发挥关键作用。

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