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早产的功能结局反映在出生后早期蛋白质组的变化中。

Preterm functional outcomes are reflected in early postnatal proteome changes.

作者信息

Zasada Magdalena, Suski Maciej, Łapińska Natalia, Pogoda Weronika, Kowalik Aleksandra, Olszewska Marta, Kwinta Przemko

机构信息

Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.

Department of Pharmacology, Jagiellonian University Medical College, Faculty of Medicine, Krakow, Poland.

出版信息

Pediatr Res. 2025 Jul 17. doi: 10.1038/s41390-025-04227-2.

DOI:10.1038/s41390-025-04227-2
PMID:40676261
Abstract

BACKGROUND

Advances in omics technologies have enabled precise analysis of protein abundance. This study applies such methods to investigate urinary proteomic quantitative changes associated with prematurity.

METHODS

Urine samples were collected from very-low-gestational-age (VLGA) infants (n = 29) without premature brain damage, as assessed using the Kidokoro scale and magnetic resonance imaging at term-equivalent age, and from full-term infants (n = 19) on the 1, 2, 3, 4, 6 and 8 days of life. SWATH-MS analysis of the urine proteome, combined with bioinformatics, was utilized for the identification of regulated urinary proteins and altered functional pathways.

RESULTS

We identified 61 proteins that were significantly differentially abundant in urine throughout the study. The regulated urinary proteins were enriched in functional domains related to the immune system, hemostasis, and complement and coagulation cascades, indicating underdevelopment in VLGA infants. Conversely, the augmented pathways included extracellular matrix organization, cholesterol metabolism and PPAR signaling.

CONCLUSIONS

The urinary proteome of VLGA infants differed significantly from that of term neonates, revealing protein profiles linked to immune system immaturity and hemostasis, altered metabolism and perturbed extracellular matrix metabolism. This study underscores how prematurity affects the urinary proteome, offering insights into the molecular pathways influenced by premature birth.

IMPACT

The urinary proteome of premature newborns differs from the urinary proteome of full-term newborns; analysis of urine proteins indicates the functional consequences of prematurity. In our study, we tested urine on the 1, 2, 3, 4, 6 and 8 days of life, which increased the reliability of the data. Examination of the urinary proteome at the first week of life allows us to demonstrate the functional consequences of prematurity. Category of study: basic science.

摘要

背景

组学技术的进步使得对蛋白质丰度进行精确分析成为可能。本研究应用此类方法来调查与早产相关的尿蛋白质组定量变化。

方法

收集孕龄极低(VLGA)婴儿(n = 29)的尿液样本,这些婴儿在足月等效年龄时经Kidokoro量表和磁共振成像评估无早产脑损伤,同时收集足月儿(n = 19)出生后第1、2、3、4、6和8天的尿液样本。利用尿液蛋白质组的SWATH-MS分析结合生物信息学来鉴定受调控的尿蛋白和改变的功能途径。

结果

在整个研究过程中,我们鉴定出61种在尿液中丰度有显著差异的蛋白质。受调控的尿蛋白在与免疫系统、止血以及补体和凝血级联相关的功能域中富集,表明VLGA婴儿存在发育不全。相反,增强的途径包括细胞外基质组织、胆固醇代谢和PPAR信号传导。

结论

VLGA婴儿的尿蛋白质组与足月儿的尿蛋白质组有显著差异,揭示了与免疫系统不成熟和止血、代谢改变以及细胞外基质代谢紊乱相关的蛋白质谱。本研究强调了早产如何影响尿蛋白质组,为受早产影响的分子途径提供了见解。

影响

早产新生儿的尿蛋白质组与足月新生儿的尿蛋白质组不同;尿液蛋白质分析表明了早产的功能后果。在我们的研究中,我们在出生后第1、2、3、4、6和8天检测尿液,这提高了数据的可靠性。在生命第一周检查尿蛋白质组使我们能够证明早产的功能后果。研究类别:基础科学。

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Complications of Preterm Birth-The Importance of Care for the Outcome: A Narrative Review.早产并发症-关注结局的重要性:一篇叙述性综述。
Medicina (Kaunas). 2024 Jun 20;60(6):1014. doi: 10.3390/medicina60061014.
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The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study.健康足月儿和稳定早产儿中性粒细胞明胶酶相关脂质运载蛋白、胱抑素C和骨桥蛋白的尿浓度:一项初步研究。
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极早产儿的短期死亡率和严重并发症——一项2019 - 2021年江苏省的多中心回顾性队列研究
Transl Pediatr. 2023 Apr 29;12(4):608-617. doi: 10.21037/tp-23-83. Epub 2023 Apr 23.
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The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome.早产儿的脑脊液蛋白质组可预测神经发育结局。
Front Pediatr. 2022 Jul 19;10:921444. doi: 10.3389/fped.2022.921444. eCollection 2022.
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Neonatology. 2022;119(2):193-203. doi: 10.1159/000520680. Epub 2022 Jan 24.
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Alpha-2-macroglobulin in hemostasis and thrombosis: An underestimated old double-edged sword.α-2-巨球蛋白在止血和血栓形成中的作用:一把被低估的古老双刃剑。
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JCI Insight. 2021 Oct 22;6(20):e138288. doi: 10.1172/jci.insight.138288.
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