Death receptor 3 is involved in preeclampsia through regulating placental trophoblast cell physiology by inactivating the PI3K/AKT pathway

Abstract

AbstractBackgroundPreeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated.ObjectiveOur research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms.MethodsHTR‐8/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR‐8/SVneo cells were analyzed via reverse transcription‐quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p‐PI3K, p‐AKT, PI3K, and AKT protein expression.ResultsUpregulation of DR3 obviously inhibited HTR‐8/SVneo cells viability, migration, and invasion, as well as promoted HTR‐8/SVneo cells apoptosis, as opposed to the control‐plasmid group. We also found that DR3‐plasmid enhanced cleaved‐caspase3 expression, reduced p‐PI3K and p‐AKT protein expression, and p‐PI3K/PI3K or p‐AKT/AKT ratio in HTR‐8/SVneo cells. Importantly, IGF‐1, a PI3K/AKT signaling pathway agonist, partially reversed the effects of DR3‐plasmid on the cell viability, migration, invasion, apoptosis, and PI3K/AKT signal pathway in HTR‐8/SVneo cells.ConclusionDR3 was involved in PE through regulating placental trophoblast cell physiology via PI3K/AKT pathway, which might be a promising therapeutic target for PE therapy.