Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China; Department of Obstetrics, S.G. Maternal and Child Health Hospital, Shouguang, China.
Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.
Exp Cell Res. 2023 Apr 15;425(2):113510. doi: 10.1016/j.yexcr.2023.113510. Epub 2023 Feb 15.
Preeclampsia (PE) is a common complication of pregnancy, usually accompanied by symptoms such as hypertension and proteinuria. It can induce severe conditions that may result in maternal and fetal morbidity and fatality. In this study, we use bioinformatics analysis to compare microRNA microassay in decidual stromal cells from PE patients and healthy donors. Our result indicated that placentas from PE patients had a higher CCL1/CXCL2 expression, compared with those from healthy donors. Bioinformatics analysis confirmed that decidual stromal cells derived from PE patients expressed significantly lower miR-455-3p than those derived from healthy donors. Transfection of miR-455-3p inhibitors enhanced the CCL2/CXCL8 expression in decidual stromal cells, and luciferase activity assay confirmed that nuclear factor of activated T cells 5 (NFAT5) mRNA was the direct target of miR-455-3p; NFAT5 also promoted cytokine secretion. In the flow cytometry study, higher M1 macrophage infiltration was observed in placentas from PE patients than in those from healthy donors. We also observed that condition medium (CM) derived from decidual stromal cells could significantly promote M1 polarization of macrophages after transfection with miR-455-3p inhibitor; further, transwell invasion assay confirmed that decidual stromal cells-CM educated macrophages suppressed trophoblast invasion. Taken together, our result demonstrates that downregulation of miR-455-3p in decidual stromal cells can promote macrophage polarization and suppress trophoblasts invasion.
子痫前期（PE）是妊娠的常见并发症，通常伴有高血压和蛋白尿等症状。它会引发严重的情况，可能导致母婴发病率和死亡率。在这项研究中，我们使用生物信息学分析比较了 PE 患者和健康供体的蜕膜基质细胞中的 microRNA 微阵列。我们的结果表明，与健康供体相比，PE 患者的胎盘 CCL1/CXCL2 表达更高。生物信息学分析证实，PE 患者的蜕膜基质细胞表达的 miR-455-3p 明显低于健康供体。转染 miR-455-3p 抑制剂增强了蜕膜基质细胞中 CCL2/CXCL8 的表达，荧光素酶活性测定证实核因子活化 T 细胞 5（NFAT5）mRNA 是 miR-455-3p 的直接靶标；NFAT5 也促进细胞因子的分泌。在流式细胞术研究中，与健康供体相比，PE 患者的胎盘中有更高比例的 M1 巨噬细胞浸润。我们还观察到，转染 miR-455-3p 抑制剂后，源自蜕膜基质细胞的条件培养基（CM）可显著促进巨噬细胞向 M1 极化；进一步的 Transwell 侵袭实验证实，蜕膜基质细胞-CM 诱导的巨噬细胞抑制滋养细胞侵袭。总之，我们的结果表明，蜕膜基质细胞中 miR-455-3p 的下调可促进巨噬细胞极化并抑制滋养细胞侵袭。
