超声和微泡介导的miR-424-5p递送对子痫前期有治疗作用。

IF 3.7 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Biological Procedures Online Pub Date : 2023-02-15 DOI:10.1186/s12575-023-00191-5
Xudong Wang, Yan Wu, Qinliang Sun, Zhonghui Jiang, Guoying Che, Yangyang Tao, Jiawei Tian
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引用次数: 1

摘要

目的:探讨超声/微泡介导的miR-424-5p传递对滋养细胞的影响及其机制。方法:测定子痫前期(PE)患者的血压、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,检测miR-424-5p、AOC1、β-catenin和c-Myc的表达以及细胞增殖、凋亡、迁移和侵袭性。测定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miR-424-5p传递的影响。结果:PE患者胎盘组织中miR-424-5p下调,AOC1上调。过表达miR-424-5p激活Wnt/β-catenin信号通路,促进HTR-8/Svneo和TEV-1细胞的增殖,增强其迁移和侵袭行为。AOC1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传递提高了miR-424-5p的转染效率,进一步促进了miR-424-5p在滋养细胞中的作用。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传递靶向AOC1,激活Wnt/β-catenin信号通路,从而促进滋养细胞的侵袭性表型,提示miR-424-5p/AOC1轴可能参与PE发病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.

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来源期刊
Biological Procedures Online
Biological Procedures Online 生物-生化研究方法
CiteScore
10.50
自引率
0.00%
发文量
16
审稿时长
>12 weeks
期刊介绍: iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.
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