Zhou Huansheng, Wang Hui, Liu Xiaohan, Liu Bei, Che Yanci, Han Rendong
Department of Obstetrics and Gynecology, Qingdao University Affiliated Hospital, Qingdao, China.
Department of Intensive Care Unit, Qingdao University Affiliated Hospital, Qingdao, China.
DNA Cell Biol. 2023 Aug;42(8):507-514. doi: 10.1089/dna.2022.0510. Epub 2023 Aug 1.
Preeclampsia (PE) is a severe pregnancy complication that accounts for about 14% of maternal deaths. Its clinical manifestations commonly include hypertension and proteinuria. However, it is largely limited in understanding its pathogenetic mechanism. In this study, we used bioinformatics to compare differential gene expressions in decidual stromal cells from PE patients and healthy donors. The result indicated that higher levels of CCL5 and CXCL2 were expressed in decidual stromal cells of PE patients compared with healthy pregnancy. The bioinformatics analysis confirmed that decidual stromal cells derived from PE patients expressed significantly lower miR-92a compared with those derived from healthy donors. Transfection of miR-92a inhibitors upregulated IL-6, CXCL2, CXCL3, CCL5, and CXCL8 expressions in decidual stromal cells. Luciferase activity assay confirmed that miR-92a directly targeted the mRNA of IRF3 whose overexpression could promote the secretion of cytokines. The flow cytometric analysis demonstrated that M1 macrophage infiltration was higher in the placentas of PE patients than in those of healthy donors. We also observed that after transfection of miR-92a inhibitor, condition medium (CM) derived from decidual stromal cells significantly promoted M1 polarization of macrophages. In addition, the transwell migration assay and flow cytometric analysis together showed that decidual stromal cell-derived CM induced macrophages to suppress the trophoblast migration and proliferation. Taken together, our result indicates that downregulation of miR-92a in decidual stromal cells promotes the macrophage polarization and suppresses the trophoblast migration and proliferation.
子痫前期（PE）是一种严重的妊娠并发症，约占孕产妇死亡的14%。其临床表现通常包括高血压和蛋白尿。然而，在很大程度上，我们对其发病机制的了解有限。在本研究中，我们使用生物信息学方法比较了PE患者和健康供体的蜕膜基质细胞中的差异基因表达。结果表明，与正常妊娠相比，PE患者的蜕膜基质细胞中CCL5和CXCL2的表达水平更高。生物信息学分析证实，与健康供体来源的蜕膜基质细胞相比，PE患者来源的蜕膜基质细胞中miR-92a的表达显著降低。转染miR-92a抑制剂可上调蜕膜基质细胞中IL-6、CXCL2、CXCL3、CCL5和CXCL8的表达。荧光素酶活性测定证实，miR-92a直接靶向IRF3的mRNA，其过表达可促进细胞因子的分泌。流式细胞术分析表明，PE患者胎盘组织中M1巨噬细胞浸润高于健康供体。我们还观察到，转染miR-92a抑制剂后，蜕膜基质细胞条件培养基（CM）显著促进巨噬细胞向M1极化。此外，Transwell迁移试验和流式细胞术分析共同表明，蜕膜基质细胞来源的CM诱导巨噬细胞抑制滋养层细胞的迁移和增殖。综上所述，我们的结果表明，蜕膜基质细胞中miR-92a的下调促进巨噬细胞极化，并抑制滋养层细胞的迁移和增殖。
