Low-dose bisphenol A impairs the function of mouse decidual stromal cells by activating LUMAN-mediated unfolded protein response
Low-dose bisphenol A impairs the function of mouse decidual stromal cells by activating LUMAN-mediated unfolded protein response
复制标题
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
DOI：
10.1016/j.fct.2021.112242
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发表时间：
2021
影响因子：
4.3
通讯作者：
Yi Yanglei
中科院分区：
文献类型：
--
作者：
Zhao Fan;Liu Huan;Li Zhanghuan;Lin Pengfei;Wang Aihua;Jin Yaping;Yi Yanglei
非甾体类雌激素化合物双酚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密封剂。由于已知双酚a具有生殖毒性，人们越来越关注这种化合物的毒性作用。本研究评估了低剂量双酚a暴露对小鼠蜕质细胞（DSCs）的影响。结果表明，虽然10 nM BPA对细胞活力没有显著影响，但它改变了脱个化相关基因prl8a2、Prl3c1、Ptgs2和mmp2的表达。此外，我们发现低剂量BPA暴露可诱导dsc的UPR反应。然而，三种主要的UPR受体（Perk、Ire 1和xbp1）的表达没有明显变化。有趣的是，一种新的UPR受体fluman的表达呈剂量依赖性显著上调。利用含有shLuman序列的慢病毒，制备了稳定的cdcs。结果表明，BPA处理后，lumanknockdown可影响蜕膜细胞蜕膜化相关基因的表达。综上所述，这些结果表明，lumana在低剂量bpa诱导的小鼠DSCs个体毒性中起关键作用。
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 includingPrl8a2,Prl3c1,Ptgs2, andMmp2. 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, andXbp1) did not change significantly. Interestingly, the expression ofLuman, a novel receptor of UPR, was significantly upregulated in a dose-dependent manner. Lentivirus containing shLuman sequence was used to generate stableLumansilencing DSCs. It's showed thatLumanknockdown could affect the expression of decidualization-related genes in decidual cells after BPA treatment. In summary, these results suggest thatLumanplays a key role in low dose BPA-induced decidual toxicity of DSCs in mouse.