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羊水过少患者羊膜中蛋白质组的改变。

Altered proteomics profile in the amnion of patients with oligohydramnios.

机构信息

Department of Obstetrics and Gynecology, Center for Developmental Health, Oregon Health and Sciences University, Portland, OR, USA.

出版信息

Physiol Rep. 2020 Feb;8(4):e14381. doi: 10.14814/phy2.14381.

Abstract

In pregnancy, idiopathic oligohydramnios is an obstetrical complication that compromises maternal health with poor perinatal outcome. Effective therapeutic treatment of this condition has been hampered by the unknown etiology and lack of understanding of cellular and molecular mechanisms that underlie idiopathic oligohydramnios. Amniotic fluid volume (AFV) is determined by intramembranous (IM) transport of amniotic fluid across the amnion and this pathway is regulated to maintain AFV within the normal range. To gain understanding of the causes of idiopathic oligohydramnios, we performed proteomics analysis of the human amnion to investigate the changes in protein expression profiles of cellular transport pathways and regulators in patients with oligohydramnios. Placental amnions from five patients with normal pregnancies and five patients with oligohydramnios were subjected to proteomics experiments followed by bioinformatics analysis. Using Ingenuity Pathway Analysis (IPA) software, five categories of biological functions and multiple canonical pathways within each category were revealed. The top differentially expressed proteins that participate in mediating these pathways were identified. The functional pathways activated include: (a) cellular assembly and organization, (b) cell signaling and energy metabolism, and (c) immunological, infectious, and inflammatory functions. Furthermore, the analysis identified the category of pathways that facilitate molecular endocytosis and vesicular uptake. Under oligohydramniotic conditions, the mediators of clathrin vesicle-mediated uptake and transport as well as intracellular trafficking mediators were up-regulated. These findings suggest that idiopathic oligohydramnios may be associated with alternations in cellular organization and immunological functions as well as increases in activity of vesicular transport pathways across the amnion.

摘要

在妊娠期间,特发性羊水过少是一种产科并发症,会影响产妇健康,导致围产儿预后不良。由于其病因不明,且对特发性羊水过少的细胞和分子机制缺乏了解,因此有效的治疗方法受到了阻碍。羊水总量(AFV)取决于羊膜内(IM)羊水跨羊膜的转运,而这一途径的调节是为了将 AFV 维持在正常范围内。为了深入了解特发性羊水过少的原因,我们对人羊膜进行了蛋白质组学分析,以研究羊水过少患者细胞转运途径和调节因子的蛋白表达谱变化。对五例正常妊娠和五例羊水过少患者的胎盘羊膜进行了蛋白质组学实验和生物信息学分析。使用 IPA 软件,揭示了五类生物学功能和每个类别中的多个经典途径。鉴定出参与调节这些途径的差异表达蛋白。激活的功能途径包括:(a)细胞组装和组织,(b)细胞信号和能量代谢,以及(c)免疫、感染和炎症功能。此外,该分析还确定了促进分子内吞作用和囊泡摄取的途径类别。在羊水过少的情况下,网格蛋白囊泡介导的摄取和转运的介质以及细胞内转运介质上调。这些发现表明,特发性羊水过少可能与细胞组织和免疫功能的改变以及羊膜内囊泡转运途径活性的增加有关。

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