基于外泌体 SUMO 蛋白表达的子痫前期新预测方法

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL

Bulletin of Russian State Medical University Pub Date : 2024-02-01 DOI:10.24075/brsmu.2024.010

VA Gusar, A. Timofeeva, IS Fedorov, A. Tarasova, YuV Suhova, TYu Ivanets

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引用次数: 0

摘要

胎盘血管功能障碍的基础是细胞对各种应激的反应受苏木酰化的控制。因此，SUMO平衡与血管生成平衡的维持密切相关，而血管生成平衡的破坏是子痫前期（PE）的一个特征。研究的目标是寻找这种疾病的外泌体标记物。研究人员利用 Western 印迹技术对外泌体 SUMO 1-4、UBC9 和 hnRNPA2/B1 的表达和预后潜力进行了评估。此外，还评估了分娩时这些蛋白质在胎盘中的表达情况（组群 II，27 名孕妇）。在早发型 PE（SUMO 1，p = 0.03；SUMO 2/3/4，p = 0.03）和晚发型 PE（SUMO 1，p = 0.03；SUMO 2/3/4，p = 0.04；UBC9 和 hnRNPA2/B1，p 分别 < 0.0001）孕妇中，这些蛋白共轭形式的表达发生了显著变化。这种变化可能是由于暴露于应激刺激时，SUMO 同工酶在其亚细胞靶标背景下的功能特异性。在胎盘中也发现了这些蛋白表达的显著变化。在早发 PE 中，外泌体 SUMO 2/3/4 （r = -0.59；p = 0.01）和 UBC9 （r = -0.88；p = 0.0001）的表达与 PlGF 之间存在显著相关性。在晚发型 PE 中，孕妇血清中的 hnRNPA2/B1 (r = -0.48; p = 0.03) 和 UBC9 (r = -0.48; p = 0.03) 与 β-hCG 相关，SUMO 2/3/4 与 PAPP-A (r = -0.60; p = 0.006)相关。所分析的蛋白质还与子宫动脉搏动指数（SUMO 1 (r = 0.59; p = 0.01)、SUMO 2/3/4 (r = 0.54; p = 0.02)、hnRNPA2/B1 (r = 0.75; p = 0.0001)）和平均动脉压（UBC9 (r = 0.53; p = 0.03)）显著相关。根据这些数据建立了逻辑模型，以预测妊娠 11-14 周时早发 PE（UBC9（AUC = 0.88；Se-0.72；Sp-1））和晚发 PE（SUMO 1（AUC = 0.79；Se-0.8；Sp-0.77））的发病风险。

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Emerging prediction of preeclampsia based on the expression of exosomal SUMO proteins

The cellular response to various types of stress underlying placental vascular dysfunction is under the sumoylation control. Consequently, SUMO homeostasis is closely related to the maintenance of angiogenic balance, the disruption of which is a feature of preeclampsia (PE). The goal of the research is to search for exosomal markers of such a disorder. The expression and prognostic potential of exosomal SUMO 1–4, UBC9 and hnRNPA2/B1 were evalueted in 39 pregnant women (cohort I) in the first trimester using Western blotting technology. The expression of these proteins in the placenta (cohort II, 27 pregnant women) at the time of delivery was also assessed. The expression of their conjugated forms was significantly changed in pregnant women with early-onset (SUMO 1, p = 0.03; SUMO 2/3/4, p = 0.03) and late-onset PE (SUMO 1, p = 0.03; SUMO 2/3/4, p = 0.04; UBC9 and hnRNPA2/B1, p < 0.0001, respectively). This change may be due to the functional specificity of SUMO isoforms in the context of their subcellular targets upon exposure to stressful stimuli. Significant changes in the expression of these proteins were also found in the placenta. Significant correlations were established between the expression of exosomal SUMO 2/3/4 (r = –0.59; p = 0.01) and UBC9 (r = –0.88; p = 0.0001) with PlGF in early-onset PE. In late-onset PE, hnRNPA2/B1 (r = –0.48; p = 0.03) and UBC9 (r = –0.48; p = 0.03) was correlated with β-hCG, and SUMO 2/3/4 with PAPP-A (r = –0.60; p = 0.006) in the blood serum of pregnant women. The analyzed proteins also significantly correlated with uterine artery pulsation index (SUMO 1 (r = 0.59; p = 0.01), SUMO 2/3/4 (r = 0.54; p = 0.02), hnRNPA2/B1 (r = 0.75; p = 0.0001)) and mean arterial pressure (UBC9 (r = 0.53; p = 0.03)). Based on the data the logistic models have been created to predict the risk of developing early-onset (UBC9 (AUC = 0.88; Se-0.72; Sp-1)) and late-onset PE (SUMO 1 (AUC = 0.79; Se-0.8; Sp-0.77)) at 11–14 weeks of pregnancy.

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Bulletin of Russian State Medical University MEDICINE, GENERAL & INTERNAL-

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0.80

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0.00%

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期刊介绍： Bulletin of Russian State Medical University (Bulletin of RSMU, ISSN Print 2500–1094, ISSN Online 2542–1204) is a peer-reviewed medical journal of Pirogov Russian National Research Medical University (Moscow, Russia). The original language of the journal is Russian (Vestnik Rossiyskogo Gosudarstvennogo Meditsinskogo Universiteta, Vestnik RGMU, ISSN Print 2070–7320, ISSN Online 2070–7339). Founded in 1994, it is issued once every two months publishing articles on clinical medicine and medical and biological sciences, first of all oncology, neurobiology, allergy and immunology, medical genetics, medical microbiology and infectious diseases. Every issue is thematic. Deadlines for manuscript submission are announced in advance. The number of publications on topics in spite of the issue topic is limited. The journal accepts only original articles submitted by their authors, including articles that present methods and techniques, clinical cases and opinions. Authors must guarantee that their work has not been previously published elsewhere in whole or in part and in other languages and is not under consideration by another scientific journal. The journal publishes only one review per issue; the review is ordered by the editors.