Downregulation of miR-455–3p in decidual cells promotes macrophage polarization and suppresses trophoblasts invasion

Abstract

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.