Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.
Biomedical Engineering, University of Strathclyde, Glasgow, U.K.
Clin Sci (Lond). 2020 Apr 30;134(8):1001-1025. doi: 10.1042/CS20200023.
Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.
胎盘 microRNAs（miRNAs）调节胎盘转录组，并在妊娠高血压疾病（PE）中发挥病理性作用。三项 PE 啮齿动物模型研究分别通过检查 miRNA、其诱导物和潜在基因靶标的表达，探讨了胎盘 miRNAs、miR-210、miR-126 和 miR-148/152 的作用。本综述通过将这三种啮齿动物模型研究的发现与体外研究、其他动物模型和子痫前期患者的发现进行比较，评估了 miR-210、miR-126 和 miR-148/152 在 PE 中的作用，从而全面了解胎盘遗传成分和病理过程对 PE 的影响。大多数研究表明，miR-210 在 PE 中上调，部分原因是 HIF-1α 和 NF-κBp50 驱动，由缺氧和/或免疫介导的过程刺激。升高的 miR-210 可能通过抑制抗炎性 Th2 细胞因子而导致 PE。研究报告 miR-126 的上调和下调，这可能反映了细胞类型之间表达的差异及其多功能能力。miR-126 可能通过调节 PI3K-Akt 通路发挥促血管生成作用。大多数研究报告 miR-148/152 家族成员在 PE 中上调。有证据表明，它们可能抑制参与代谢和炎症途径的基因的 DNA 甲基化。鉴于 PE 的遗传异质性，单一胎盘 miRNA 不太可能成为所有患者的合适治疗靶点。在患者和动物模型中研究 PE 亚型中的 miRNAs 可能是未来更合适的方法。开发针对胎盘 miRNAs 和特定胎盘细胞类型的方法对于以胎盘 miRNAs 为靶点作为治疗 PE 的新方法的研究仍然至关重要。
