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首页> 外文期刊>Human and Experimental Toxicology >MicroRNA-155 is upregulated in the placentas of patients with preeclampsia and affects trophoblast apoptosis by targeting SHH/GLi1/BCL2
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MicroRNA-155 is upregulated in the placentas of patients with preeclampsia and affects trophoblast apoptosis by targeting SHH/GLi1/BCL2

机译：MicroRNA-155在患有先兆子痫患者的胎盘上上调，并通过靶向SHH / GLI1 / BCL2影响滋养细胞凋亡

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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.
机译：先兆子痫（PE）的发病机制复杂，其发生与多种危险因素有关。然而，涉及PE的潜在分子机制仍然难以捉摸。已经观察到异常的细胞凋亡和滋养层浸润不足，被认为是PE的重要病理特征。在此，我们通过双荧光素酶报告分析发现miR-155可以特异性降解刺猬配体sonic Hedgehog（SHH）的mRNA。定量实时PCR发现，施用miR-155模拟物或抑制剂可分别显著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。通过受试者操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。在体外培养的HTR8/SVneo细胞中施用miR-155后，观察到凋亡显著增加，同时增殖减少。机制上，在miR-155治疗下，GLi1的转录活性和表达也受到抑制，并且在向患者的原发性滋养层细胞提供额外的重组人SHH后，可以恢复，如荧光素酶活性测定和western印迹所确定。我们进一步发现，抑制miR-155可增加PE患者原发性滋养层中SHH的产生，并改善其表型。我们的数据显示，miR-155调节PE中滋养层细胞的凋亡，这对预测PE风险具有潜在价值，可能被视为治疗PE的治疗靶点。

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