妊娠期糖尿病中抗氧化反应相关微小RNA miR-146a-5p和miR-21-5p的上调：细胞外囊泡与外周血单个核细胞匹配样本的分析

Upregulation of the Antioxidant Response-Related microRNAs miR-146a-5p and miR-21-5p in Gestational Diabetes: An Analysis of Matched Samples of Extracellular Vesicles and PBMCs.

作者信息

Stevanović Jovana, Mitić Ninoslav, Penezić Ana, Radojičić Ognjen, Ardalić Daniela, Mandić Milica, Mandić-Marković Vesna, Miković Željko, Brkušanin Miloš, Nedić Olgica, Dobrijević Zorana

机构信息

Institute for the Application of Nuclear Energy, University of Belgrade, 11080 Belgrade, Serbia.

Clinic for Gynecology and Obstetrics "Narodni Front", 11000 Belgrade, Serbia.

出版信息

Int J Mol Sci. 2025 Jul 18;26(14):6902. doi: 10.3390/ijms26146902.

DOI:10.3390/ijms26146902

PMID:40725161

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12295923/

Abstract

MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by using peripheral blood mononuclear cells (PBMCs) and serum-derived extracellular vesicles (EVs) as biological samples. We selected the known OS/IFM-associated microRNAs miR-146a-5p, miR-155-5p, and miR-21-5p as candidates for our GDM biomarker analysis. Quantitative RT-PCR was employed for relative quantification of the selected microRNAs from paired samples of PBMCs and EVs derived from patients with GDM and healthy controls ( = 50 per group). The expression levels were analyzed for correlations with lipid and glycemic status indicators; metal ion-related parameters; serum thiol content; protein carbonyl and thiobarbituric acid-reactive substances' (TBARS) levels; glutathione reductase (GR), Superoxide dismutase (SOD), and catalase (CAT) activity; and NRF2 expression. MiR-146a-5p and miR-21-5p were significantly upregulated in both PBMCs and EVs obtained from GDM patients. EVs-miR-21-5p showed a positive correlation with glycemic status in GDM patients, while miR-155-5p from PBMCs demonstrated correlation with iron-related parameters. The expression of selected microRNAs was found to correlate with NRF2 expression and SOD activity. The level of miR-146a-5p negatively correlated with neonatal anthropometric characteristics, while a higher level of PBMCs-miR-21-5p expression was determined in GDM patients with adverse pregnancy outcomes ( = 0.012). Our data demonstrate a disturbance of OS/IFM-microRNAs in GDM and illustrate their potential to serve as indicators of the associated OS-related changes, neonatal characteristics, and adverse pregnancy outcomes.

摘要

基于微小RNA的调控机制显示出与氧化应激（OS）相关的紊乱，氧化应激与炎症（IFM）相互关联，同时也存在与妊娠期糖尿病（GDM）相关的损伤。本研究的目的是通过使用外周血单个核细胞（PBMCs）和血清来源的细胞外囊泡（EVs）作为生物样本，评估与OS/IFM相关的微小RNA在GDM中的诊断和预后意义。我们选择已知的与OS/IFM相关的微小RNA miR-146a-5p、miR-155-5p和miR-21-5p作为GDM生物标志物分析的候选物。采用定量逆转录聚合酶链反应（qRT-PCR）对来自GDM患者和健康对照（每组n = 50）的PBMCs和EVs配对样本中选定的微小RNA进行相对定量。分析了表达水平与脂质和血糖状态指标、金属离子相关参数、血清硫醇含量、蛋白质羰基和硫代巴比妥酸反应性物质（TBARS）水平、谷胱甘肽还原酶（GR）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及NRF2表达的相关性。在从GDM患者获得的PBMCs和EVs中，miR-146a-5p和miR-21-5p均显著上调。EVs-miR-21-5p与GDM患者的血糖状态呈正相关，而PBMCs中的miR-155-5p与铁相关参数相关。发现选定的微小RNA的表达与NRF2表达和SOD活性相关。miR-146a-5p水平与新生儿人体测量特征呈负相关，而在妊娠结局不良的GDM患者中，PBMCs-miR-21-5p表达水平较高（P = 0.012）。我们的数据表明GDM中存在OS/IFM-微小RNA的紊乱，并说明了它们作为相关OS相关变化、新生儿特征和不良妊娠结局指标的潜力。