Transcription Factor FOXD3 Regulates ELAV1/TLR4 Axis in Antiphospholipid Syndrome to Mediate Proliferation and Migration of Trophoblasts

Abstract

This study focused on exploring the mechanism of transcription factor FOXD3 promoting the proliferation, migration, and invasion of trophoblast through ELAV1/TLR4 axis. The placenta villi from pregnancy patients with antiphospholipid syndrome (APS) and pregnancy controls were collected, along with the HTR-8/SVneo cell lines were obtained to detect the FOXD3, ELAV1, and TLR4 expressions using qRT-PCR and western blot. The interaction of ELAV1 with TLR4 mRNA was verified using RNA immunoprecipitation. The binding of FOXD3 with ELAV1 was detected using Chromatin Immunoprecipitation and dual luciferase reporter gene assay. After cell transfection, the cell proliferation, cell cycle distribution, invasion, and migration of the HTR-8/SVneo cell line were also measured. FOXD3, ELAV1, and TLR4 were elevated in the placenta villi of APS patients. TLR4 knockdown can promote the proliferation, invasion, and migration ability of HTR-8/SVneo cells. ELAV1 can bind TLR4 mRNA and increase its stability. TLR4 overexpression can inhibit the promotive effect of ELAV1 knockdown on HTR-8/SVneo cell biological functions. FOXD3 can bind the ELAV1 promoter and increase its transcription level to mediate HTR-8/SVneo cell biological functions. FOXD3 can bind and increase ELAV1 expression to stabilize TLR4 mRNA level, thereby increasing TLR4 expression and inhibiting the proliferation, invasion, and migration ability of trophoblast.