MiR-940-IL-32β-polymorphonuclear neutrophils pathway inhibits trophoblast cell invasion and induces inflammatory responses

Abstract

The involvement of microRNA (miRNA) is of paramount importance in regulating the advancement of preeclampsia. Activating the immune system at the interface between the mother and fetus significantly contributes to the development of pre-eclampsia (PE). The activation of polymorphonuclear neutrophils (PMNs) in patients with PE necessitates additional investigation to elucidate the underlying mechanism of PMNs activation. The present work has revealed the downregulation of miR-940 expression in the plasma exosomes of individuals diagnosed with preeclampsia, which is closely related to the increased invasion of trophoblastic cells and the induction of clinical symptoms related to inflammatory responses. The upregulation of interleukin-32 (IL-32) expression is notably observed in syncytiotrophoblast cells, with interleukin-32β(IL-32β) being the primary isoform exhibiting higher expression in the placenta of individuals diagnosed with PE. In vitro investigations indicate that IL-32β exhibits a significant capacity to activate PMNs. We identified IL-32β as a direct target of miR-940 through gene expression profiling and bioinformatics analysis. Patients with low miR-940 expression, high IL-32β level, and increased PMN number had more complications and poor perinatal prognosis. Conclusion: miR-940-IL-32β-neutrophil feedback loop inhibits trophoblast invasion and induces inflammatory response.