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超声与微泡介导的miR-424-5p递送对先兆子痫具有治疗作用。

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

作者信息

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

机构信息

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang, 150001, P.R. China.

出版信息

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

DOI:10.1186/s12575-023-00191-5
PMID:36788514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9930350/
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.

摘要

目的

确定超声/微泡介导的miR-424-5p递送对滋养层细胞的影响及其潜在机制。

方法

测量子痫前期（PE）患者的血压和24小时蛋白尿，以及胎盘组织中miR-424-5p和含铜胺氧化酶1（AOC1）的水平。对HTR-8/Svneo和TEV-1细胞进行细胞转染或超声微泡转染，以测定miR-424-5p、AOC1、β-连环蛋白和c-Myc的表达以及细胞增殖、凋亡、迁移和侵袭能力。检测HTR-8/Svneo和TEV-1细胞中胎盘生长因子（PLGF）、人绒毛膜促性腺激素（β-hCG）和肿瘤坏死因子-α（TNF-α）的浓度。RNA免疫沉淀（RIP）和双荧光素酶报告基因检测法检测miR-424-5p与AOC1的结合。通过皮下注射L-NAME诱导PE小鼠模型，评估超声/微泡介导的miR-424-5p递送的影响。

结果

PE患者胎盘组织中miR-424-5p下调而AOC1上调。miR-424-5p的过表达激活Wnt/β-连环蛋白信号通路，促进HTR-8/Svneo和TEV-1细胞的增殖，并增强其迁移和侵袭行为。AOC1的过表达部分消除了miR-424-5p对HTR-8/Svneo和TEV-1细胞的影响。超声和微泡介导的基因递送提高了miR-424-5p的转染效率，并进一步促进了miR-424-5p在滋养层细胞中的作用。超声/微泡介导的miR-424-5p递送减轻了小鼠实验性PE。

结论

超声和微泡介导的miR-424-5p递送靶向AOC1并激活Wnt/β-连环蛋白信号通路，从而促进滋养层细胞的侵袭性表型，这表明miR-424-5p/AOC1轴可能参与PE的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/f1bc9b7c9cb0/12575_2023_191_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/588f92057ba7/12575_2023_191_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/ea14f97a0099/12575_2023_191_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/f1bc9b7c9cb0/12575_2023_191_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/588f92057ba7/12575_2023_191_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/29d665249933/12575_2023_191_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/d2d3d2fb4c80/12575_2023_191_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/100ca6ef5cbb/12575_2023_191_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/5f79591e006c/12575_2023_191_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/ea14f97a0099/12575_2023_191_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ca/9930350/f1bc9b7c9cb0/12575_2023_191_Fig8_HTML.jpg

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