The pathogenesis of preeclampsia (PE) is complicated and multiple risk factors have been associated with its occurrence. Still, the underlying molecular mechanisms involved in PE remain elusive. Aberrant apoptosis and insufficient invasion of trophoblasts have been observed and are considered vital pathological features in PE. Herein, we found that miR-155 can specifically degrade the mRNA of the Hedgehog ligand sonic hedgehog (SHH), using dual luciferase reporter assays. Quantitative real-time PCR found that administering miR-155 mimics or inhibitors could significantly decrease or increase the expression of SHH in the trophoblasts, respectively. The transcription levels of miR-155 in the placenta were higher in patients with PE compared to the levels in healthy pregnant women, as shown by quantitative real-time PCR. Serum levels of miR-155 could predict the diagnosis of PE by receiver operating characteristic curve analysis and diagnosis evaluation tests. A significant increase in apoptosis was observed after administering miR-155 in HTR8/SVneo cells cultured ex vivo, accompanied by reduced proliferation. Mechanistically, transcriptional activity and expression of GLi1 were also inhibited under treatment of miR-155, and could be recovered after supplying additional recombinant human SHH to primary trophoblasts from patients, as determined by luciferase activity assays and western blotting. We further found that inhibiting miR-155 increased the production of SHH and improved the phenotype in primary trophoblasts from patients with PE. Our data show that miR-155 regulates apoptosis of trophoblasts in PE, which has potential value for predicting PE risk and might be deemed as a therapeutic target for treating PE.

先兆子痫（PE）的发病机制复杂，多种危险因素与其发生有关。尽管如此，PE 的潜在分子机制仍然难以捉摸。异常的细胞凋亡和滋养细胞的侵袭不足已被观察到，并被认为是 PE 的重要病理特征。在此，我们使用双荧光素酶报告基因检测发现 miR-155 可以特异性降解 Hedgehog 配体 sonic humility (SHH) 的 mRNA。定量实时PCR发现，给予miR-155模拟物或抑制剂可以分别显着降低或增加滋养层中SHH的表达。实时定量 PCR 显示，PE 患者胎盘中 miR-155 的转录水平高于健康孕妇。通过受试者工作特征曲线分析和诊断评估试验，血清miR-155水平可以预测PE的诊断。在离体培养的 HTR8/SVneo 细胞中给予 miR-155 后，观察到细胞凋亡显着增加，同时增殖减少。从机制上讲，GLi1 的转录活性和表达在 miR-155 的治疗下也受到抑制，并且通过荧光素酶活性测定和蛋白质印迹确定，在向患者的初级滋养层提供额外的重组人 SHH 后可以恢复。我们进一步发现，抑制 miR-155 会增加 SHH 的产生，并改善 PE 患者初级滋养层细胞的表型。我们的数据表明，miR-155 调节 PE 中滋养细胞的凋亡，这对于预测 PE 风险具有潜在价值，并可能被视为治疗 PE 的治疗靶点。