超声和微泡介导的miR-424-5p递送在子痫前期中具有治疗效果。
Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia.
发表日期:2023 Feb 15
作者:
Xudong Wang, Yan Wu, Qinliang Sun, Zhonghui Jiang, Guoying Che, Yangyang Tao, Jiawei Tian
来源:
BIOLOGICAL PROCEDURES ONLINE
摘要:
为确定超声/微泡介导miR-424-5p传递对滋养层细胞的影响及其潜在机制,本研究测量了子痫前患者(PE)的血压和24小时蛋白尿水平以及胎盘组织中miR-424-5p和含铜脲酶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,以确定miR-424-5p、AOC1、β-连环蛋白和c-Myc的表达,以及细胞增殖、凋亡、迁移和侵袭性。测量了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)和双荧光素酶报告实验检测miR-424-5p对AOC1的结合。通过皮下注射L-NAME诱导子痫前小鼠模型,评估了超声/微泡介导miR-424-5p传递对其的影响。miR-424-5p在PE患者的胎盘组织中下调,而AOC1上调。miR-424-5p的过表达激活了Wnt/β-连环蛋白信号通路,促进了HTR-8 / Svneo和TEV-1细胞的增殖,并增强了迁移和侵袭行为。 AOC1的过表达在一定程度上消除了miR-424-5p对HTR-8 / Svneo和TEV-1细胞的影响。超声和微泡介导基因转染增强了miR-424-5p的转染效率,并进一步促进了miR-424-5p对滋养层细胞的作用。超声/微泡介导miR-424-5p传递缓解了小鼠实验性PE。超声和微泡介导的miR-424-5p传递靶向AOC1并激活Wnt/β-连环蛋白信号通路,从而促进了滋养层细胞的侵袭性表型,这表明miR-424-5p / AOC1轴可能与PE的病理机制有关。 © 2023。作者(们)。
To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism.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.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.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.© 2023. The Author(s).