Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia

ObjectiveTo determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism.MethodsBlood pressure and 24-h proteinuria of patients with preeclampsia (PE) were measured as well as the levels of miR-424-5p and amine oxidase copper containing 1 (AOC1) in placental tissues. HTR-8/Svneo and TEV-1 cells were subjected to cell transfection or ultrasonic microbubble transfection for determination of the expression of miR-424-5p, AOC1, beta-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (beta-hCG) and tumor necrosis factor-alpha (TNF-alpha) were measured in HTR-8/Svneo and TEV-1 cells. RNA immunoprecipitation (RIP) and dual luciferase reporter assay detected the binding of miR-424-5p to AOC1. A PE mouse model was induced by subcutaneous injection of L-NAME, where the influence of ultrasound/microbubble-mediated miR-424-5p delivery was evaluated.ResultsmiR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/beta-catenin signaling pathway and promoted the proliferation of HTR-8/Svneo and TEV-1 cells as well as enhanced the migratory and invasive behaviors. AOC1 overexpression partly eliminated the effects of miR-424-5p on HTR-8/Svneo and TEV-1 cells. Ultrasound and microbubble mediated gene delivery enhanced the transfection efficiency of miR-424-5p and further promoted the effects of miR-424-5p in trophoblast cells. Ultrasound/microbubble-mediated miR-424-5p delivery alleviated experimental PE in mice.ConclusionUltrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/beta-catenin signaling pathway, thus promoting the aggressive phenotype of trophoblast cells, which indicating that miR-424-5p/AOC1 axis might be involved with PE pathogenesis.

Automated summary

The study aimed to investigate the influence of ultrasound/microbubble-mediated delivery of miR-424-5p on trophoblast cells and its underlying mechanism. The results showed that miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues of patients with preeclampsia. Overexpression of miR-424-5p activated the Wnt/beta-catenin signaling pathway and promoted the proliferation, migration, and invasiveness of trophoblast cells. Ultrasound/microbubble-mediated delivery of miR-424-5p enhanced the transfection efficiency and further promoted the effects of miR-424-5p in trophoblast cells. It also alleviated experimental preeclampsia in a mouse model.