Effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia in vitro
Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia,and to search possible targets for early diagnosis and prevention of preeclampsia.Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital,Fudan University from October 2021 to December 2022.The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR.Cell transfection was performed by lipofectamine 2000 in vitro.The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay.The apoptosis of neutrophils,the migration,repair,colony formation and cell-free DNA(cfDNA)release of human umbilical vein endothelial cells(HUVECs)were detected.Results MiR-4531 was significantly downregulated,and CX3CL1 was upregulated in placental tissues of preeclampsia patients(P<0.05).Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1.Upregulation of miR-4531significantly promoted the migration,proliferation,repair,and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition(P<0.05).However,downregulation of miR-4531 obviously inhibited the proliferation,migration,repair,and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition(P<0.05).Conclusions The miR-4531 is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia.It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.
preeclampsiamiR-4531CX3CL1human umbilical vein endothelial cellcell-free DNA