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

Xudong Wang; Yan Wu; Qinliang Sun; Zhonghui Jiang; Guoying Che; Yangyang Tao; Jiawei Tian

doi:10.1186/s12575-023-00191-5

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

Biol Proced Online. 2023 Feb 15;25(1):3. doi: 10.1186/s12575-023-00191-5.

Authors

Xudong Wang¹, Yan Wu¹, Qinliang Sun¹, Zhonghui Jiang¹, Guoying Che¹, Yangyang Tao¹, Jiawei Tian²

Affiliations

¹ Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang, 150001, P.R. China.
² Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang, 150001, P.R. China. jwtian2004@163.com.

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.

Keywords: AOC1; Invasion; Migration; Preeclampsia; Trophoblast cells; Ultrasound and microbubble mediated gene delivery; miR-424-5p.