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早产儿和足月儿脐带间充质干细胞来源微泡的代谢特征

Metabolic Signature of Microvesicles from Umbilical Cord Mesenchymal Stem Cells of Preterm and Term Infants.

作者信息

Bruschi Maurizio, Santucci Laura, Ravera Silvia, Bartolucci Martina, Petretto Andrea, Calzia Daniela, Ghiggeri Gian Marco, Ramenghi Luca A, Candiano Giovanni, Panfoli Isabella

机构信息

Laboratory of Molecular Nephrology Istituto Giannina Gaslini, Genoa, Italy.

Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy.

出版信息

Proteomics Clin Appl. 2018 May;12(3):e1700082. doi: 10.1002/prca.201700082. Epub 2017 Dec 5.

Abstract

PURPOSE

Microvesicles (MVs), 200-1000 nm bodies budding from the cell plasma membrane, are a promising source of biomarkers. This study aimed at comparing the proteome of MVs collected by ultracentrifugation from cultured Mesenchymal Stem Cells (MSCs) from Human Umbilical Cord of Preterm newborns (<34-weeks gestational age) in comparison to infants at Term (≥37 weeks). This discovery study was designed to establish the signature of prematurity.

EXPERIMENTAL DESIGN

Orbitrap MS, statistical, bioinformatics and biochemical analyses were employed.

RESULTS

A total of 3253 proteins were identified, 78.3% matching among Preterm and Term. Principal component dimensional analyses showed that the two proteomes cluster separately. Cytoscape analysis showed that the top gene signatures cluster around inflammation and oxidative metabolism. Both Preterm and Term MVs consumed oxygen, and express ATP synthase and cytochrome oxidase, but only Preterm MVs synthesized ATP. The gene signature of Preterm condition mainly clusters around inflammation and metabolism.

CONCLUSION AND CLINICAL RELEVANCE

MVs from MSCs conduct aerobic metabolism similarly to exosomes from the same cells, with interesting differences related to their biogenesis and function. The clinical relevance of the study lays in the perspective to utilize MVs as promising sensor of the inflammatory and metabolic state of the preterm newborn, to help in preventing the complications of prematurity.

摘要

目的

微泡(MVs)是从细胞质膜上芽生出的200 - 1000纳米的小体,是一种很有前景的生物标志物来源。本研究旨在比较通过超速离心从孕周小于34周的早产儿脐带间充质干细胞(MSCs)培养物中收集的微泡蛋白质组,与足月儿(孕周≥37周)的微泡蛋白质组。这项探索性研究旨在确定早产的特征。

实验设计

采用了轨道阱质谱、统计学、生物信息学和生化分析方法。

结果

共鉴定出3253种蛋白质,其中78.3%在早产儿和足月儿中匹配。主成分维度分析表明,这两种蛋白质组分别聚类。Cytoscape分析表明,顶级基因特征围绕炎症和氧化代谢聚类。早产儿和足月儿的微泡都消耗氧气,并表达ATP合酶和细胞色素氧化酶,但只有早产儿的微泡合成ATP。早产状态的基因特征主要围绕炎症和代谢聚类。

结论及临床意义

间充质干细胞来源的微泡与同一细胞来源的外泌体进行类似的有氧代谢,在生物发生和功能方面存在有趣的差异。该研究的临床意义在于有望将微泡用作早产儿炎症和代谢状态的传感器,以帮助预防早产并发症。

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