Brooks Samira A, Fry Rebecca C
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, 135 Dauer Drive, CB 7431, University of North Carolina, Chapel Hill, NC, USA.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, 135 Dauer Drive, CB 7431, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Food Chem Toxicol. 2017 Nov;109(Pt 1):721-726. doi: 10.1016/j.fct.2017.07.059. Epub 2017 Aug 1.
Preeclampsia (PE), a condition during pregnancy that involves high blood pressure and proteinuria, is potentially fatal to both mother and child. PE currently has no known etiology or cure but has been tied to poor placental trophoblast cell migration. Increased levels of the toxic metal cadmium (Cd) have been associated with increased risk of developing PE, as well as miRNA-associated regulation of the transforming growth factorbeta (TGF-β) pathway. Signal reprogramming of the TGF-β pathway via epigenetic mechanisms is hypothesized to modify placental trophoblast function. In the present study we investigated the role of increased and decreased signaling of the TGF-β pathway in relation to Cd-induced reduction in cellular migration in JEG3 trophoblast cells. Furthermore, the role of a miR-26a as a molecular mediator of placental trophoblast migration was confirmed. The results demonstrate that increased expression of miR-26a and decreased signaling of the TGF-β pathway increase placental cell migration. These findings have relevance for mechanistic understanding of the underpinnings of poor placentation associated with PE.
子痫前期（PE）是一种孕期疾病，伴有高血压和蛋白尿，对母婴都有潜在致命风险。目前PE的病因不明，也无法治愈，但与胎盘滋养层细胞迁移不良有关。有毒金属镉（Cd）水平升高与患PE风险增加有关，同时也与微小RNA（miRNA）对转化生长因子β（TGF-β）通路的调控有关。据推测，通过表观遗传机制对TGF-β通路进行信号重编程可改变胎盘滋养层细胞功能。在本研究中，我们调查了TGF-β通路信号增强和减弱与Cd诱导的JEG3滋养层细胞迁移减少之间的关系。此外，还证实了miR-26a作为胎盘滋养层细胞迁移分子介质的作用。结果表明，miR-26a表达增加和TGF-β通路信号减弱会增加胎盘细胞迁移。这些发现对于从机制上理解与PE相关的胎盘形成不良的基础具有重要意义。
