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微小RNA-203a-3p通过调控白细胞介素24抑制子痫前期的炎症反应。

MiRNA-203a-3p inhibits inflammatory response in preeclampsia through regulating IL24.

作者信息

Ma H-Y, Cu W, Sun Y-H, Chen X

机构信息

Department of Obstetrics, Zibo Maternal and Child Health Hospital, Zibo, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 May;24(10):5223-5230. doi: 10.26355/eurrev_202005_21304.

DOI:10.26355/eurrev_202005_21304
PMID:32495855
Abstract

OBJECTIVE

This study aims to investigate the protective role of miRNA-203a-3p in preeclampsia (PE) patients via inhibiting the inflammatory key protein IL24.

PATIENTS AND METHODS

Serum samples of 36 PE pregnant women and 30 normal pregnant volunteers hospitalized between 2015 and 2019 were collected to extract placental mononuclear cells and exosomes. Relative levels of microRNA-203a-3p and IL24 were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). In addition, the interaction between microRNA-203a-3p and IL24 was analyzed through bioinformatics analysis and Luciferase reporting assay. Finally, the underlying molecular mechanisms were further explored via immunofluorescence and Western blotting.

RESULTS

Compared with normal pregnant volunteers, microRNA-203a-3p expression in serum exosomes and placental mononuclear cells of PE patients were dramatically reduced, while IL24 was conversely up-regulated, indicating a negative correlation between microRNA-203a-3p and IL24 levels. In addition, IL24, which was down-regulated in mononuclear macrophages overexpressing microRNA-203a-3p, was indicated as a target of microRNA-203a-3p. At the same time, microRNA-203a-3p was able to suppress the proliferation capacity of LPS-stimulated mononuclear macrophages, and it exerted anti-inflammatory effects via down-regulating IL24 in THP-1 cells.

CONCLUSIONS

MicroRNA-203a-3p plays an anti-inflammatory role in PE pregnant women by down-regulating IL24 level.

摘要

目的

本研究旨在通过抑制炎症关键蛋白IL24来探讨miRNA - 203a - 3p在子痫前期(PE)患者中的保护作用。

患者与方法

收集2015年至2019年期间住院的36例PE孕妇和30例正常妊娠志愿者的血清样本,以提取胎盘单核细胞和外泌体。通过定量实时聚合酶链反应(qRT - PCR)检测微小RNA - 203a - 3p和IL24的相对水平。此外,通过生物信息学分析和荧光素酶报告基因检测分析微小RNA - 203a - 3p与IL24之间的相互作用。最后,通过免疫荧光和蛋白质印迹进一步探索潜在的分子机制。

结果

与正常妊娠志愿者相比,PE患者血清外泌体和胎盘单核细胞中微小RNA - 203a - 3p的表达显著降低,而IL24则相反上调,表明微小RNA - 203a - 3p与IL24水平呈负相关。此外,在过表达微小RNA - 203a - 3p的单核巨噬细胞中下调的IL24被表明是微小RNA - 203a - 3p的靶标。同时,微小RNA - 203a - 3p能够抑制LPS刺激的单核巨噬细胞的增殖能力,并通过下调THP - 1细胞中的IL24发挥抗炎作用。

结论

微小RNA - 203a - 3p通过下调IL24水平在PE孕妇中发挥抗炎作用。

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