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

Abstract

Objective To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism. Methods Blood 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, β-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (β-hCG) and tumor necrosis factor-α (TNF-α) 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. Results miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/β-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. Conclusion Ultrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/β-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.

Suppression of circular RNA serum and glucocorticoid‐induced kinase 1 elevates antioxidant molecules and angiogenesis in trophoblast cells to attenuate preeclampsia via microRNA‐508‐3p to target and restrain PUM homolog 1

“…The next morning, vaginal smears were performed on female rats to verify sperm on day 0 of gestation. The PE rat model was established by subcutaneous injection of NG‐nitro‐L‐arginine methyl ester (L‐NAME) 32,33 . Different working groups have previously established the PE‐like model that has been used in this study 34–36 .…”

“…The PE rat model was established by subcutaneous injection of NG-nitro-L-arginine methyl ester (L-NAME). 32,33 Different working groups have previously established the PElike model that has been used in this study. [34][35][36] It is induced by the administration of L-NAME, which is an inhibitor of NO production, as it inhibits the NOS enzyme, prevents endothelium-dependent relaxation, and produces an increase in the blood pressure.…”