miRNAs as common regulators of the transforming growth factor (TGF)-β pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia.
miRNAs as common regulators of the transforming growth factor (TGF)-β pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia.
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DOI：
10.1016/j.fct.2016.06.023
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Fry RC
中科院分区：
文献类型：
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作者：
Brooks SA;Martin E;Smeester L;Grace MR;Boggess K;Fry RC
子痫前期(PE)是一种以高血压和蛋白尿为特征的妊娠疾病，可对母亲和胎儿造成不利的健康影响。除了分娩外，目前还没有治疗PE的方法。虽然病因不明，但由于生长信号和血管生成因子的异常信号导致的胎盘不良已被认为是PE的原因。此外，环境污染物，如金属镉(Cd)，已被认为与胎盘毒性和增加发生PE的风险有关。在这里，我们使用翻译研究设计来研究胎盘和胎盘滋养层细胞的基因组和表观基因组的变化，重点是血管生成相关的转化生长因子-β(β)途径。转化生长因子-β途径中的基因在先兆子痫胎盘和镉处理的滋养层细胞中的表达均增加。此外，靶向转化生长因子-β途径的miRNA在先兆子痫胎盘和镉处理的滋养层细胞中也发生了显著变化。综合分析的结果是鉴定了镉反应miRNAs的一个子集，包括miR-26a和miR-155，它们是先兆子痫胎盘和镉处理的滋养层细胞共同的。这些miRNAs以前被连接到PE，并被预测调节转化生长因子-β途径的成员。这项研究的结果为PE治疗提供了未来的靶点。
Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is no current cure for PE other than delivery of the fetus. While the etiology is unknown, poor placentation of the placenta due to aberrant signaling of growth and angiogenic factors has been postulated as causal factors of PE. In addition, environmental contaminants, such as the metal cadmium (Cd), have been linked to placental toxicity and increased risk of developing PE. Here, we use a translational study design to investigate genomic and epigenomic alterations in both placentas and placental trophoblasts, focused on the angiogenesis-associated transforming growth factor-beta (TGF-β) pathway. Genes within the TGF-β pathway displayed increased expression in both the preeclamptic placenta and Cd-treated trophoblasts. In addition, miRNAs that target the TGF-β pathway were also significantly altered within the preeclamptic placenta and Cd-treated trophoblasts. Integrative analysis resulted in the identification of a subset of Cd-responsive miRNAs, including miR-26a and miR-155, common to preeclamptic placentas and Cd-treated trophoblasts. These miRNAs have previously been linked to PE and are predicted to regulate members of the TGF-β pathway. Results from this study provide future targets for PE treatment.