Human umbilical cord mesenchymal stem cells (MSCs) have been reported to improve the migration and invasion of trophoblast cells; however, little is known about whether MSC-derived exosomes and exosomal miRNAs can regulate trophoblast cell properties. In this study, we investigated whether exosomal miRNAs from amniotic fluid-derived MSC (AF-MSC) could regulate the inflammatory response of the human trophoblast cell line HTR8/SVneo. We verified the anti-inflammatory effects of AF-MSCs on lipopolysaccharide (LPS)-induced inflammatory trophoblast cells and found that miR-146a-5p and miR-548e-5p in the AF-MSC-derived exosomes regulate nuclear factor κB, AKT and mitogen-activated protein kinase protein phosphorylation. Furthermore, we found that the transfection of human trophoblast cells with miR-146a-5p and miR-548e-5p inhibitors reduced trophoblast migration (P < 0.05 vs control) and the expression of proliferating cell nuclear antigen, a protein essential for cell proliferation (P < 0.01 vs control). In particular, the miR-548e-5p inhibitor induced apoptosis, while tumor necrosis factor receptor-associated factor 6, a predicted target of miR-146a-5p and miR-548e-5p, was involved in the regulation of oxidative stress in the human trophoblast cells. In a mouse model of LPS-induced preterm birth (PB), miR-146a-5p expression was found to be relatively low in the group in which the effect of AF-MSCs was insignificant. However, this study is limited in that the changes in the expression of some genes in response to AF-MSCs differ between the cell line and mouse model. Collectively, these data show that exosomal miR-146a-5p and miR-548e-5p from AF-MSCs have anti-inflammatory effects on human trophoblast cells and may be novel targets for treating inflammatory diseases and associated problems that occur during pregnancy, such as PB.

中文翻译：

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间充质干细胞来源的外泌体microRNA-146a-5p和microRNA-548e-5p对人滋养细胞的抗炎作用。

据报道，人脐带间充质干细胞（MSC）可以改善滋养层细胞的迁移和侵袭。然而，关于MSC来源的外泌体和外泌体miRNA是否能调节滋养细胞的特性还知之甚少。在这项研究中，我们调查了羊水来源的MSC（AF-MSC）的外泌体miRNA是否可以调节人滋养细胞HTR8 / SVneo细胞的炎症反应。我们验证了AF-MSC对脂多糖（LPS）诱导的炎性滋养层细胞的抗炎作用，发现AF-MSC衍生的外泌体中的miR-146a-5p和miR-548e-5p调节核因子κB，AKT和有丝分裂原激活的蛋白激酶蛋白磷酸化。此外，我们发现，用miR-146a-5p和miR-548e-5p抑制剂转染人滋养层细胞可减少滋养层迁移（与对照相比，P <0.05）和增殖细胞核抗原（一种对细胞增殖至关重要的蛋白质）的表达（P < 0.01 vs. 特别是，miR-548e-5p抑制剂诱导细胞凋亡，而肿瘤坏死因子受体相关因子6（miR-146a-5p和miR-548e-5p的预期靶标）参与了人类氧化应激的调节。滋养细胞。在LPS诱导的早产（PB）的小鼠模型中，发现在AF-MSC的影响不明显的组中，miR-146a-5p表达相对较低。然而，这项研究的局限性在于，在细胞系和小鼠模型之间，某些基因对AF-MSCs的响应发生了变化。