Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus.
Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus.
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细胞外囊泡相关mirna是对妊娠糖尿病的适应性反应。
DOI：
10.1186/s12967-021-02999-9
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发表时间：
2021-08-20
影响因子：
7.4
通讯作者：
Salomon C
中科院分区：
文献类型：
--
作者：
Nair S;Guanzon D;Jayabalan N;Lai A;Scholz-Romero K;Kalita de Croft P;Ormazabal V;Palma C;Diaz E;McCarthy EA;Shub A;Miranda J;Gratacós E;Crispi F;Duncombe G;Lappas M;McIntyre HD;Rice G;Salomon C
妊娠期糖尿病（GDM）是一种严重的公共卫生问题，影响全球所有妊娠的9-15%。最近，有人提出，细胞外囊泡（EV）在整个妊娠过程中发挥作用，包括介导胎盘对高脂血症的反应。在这里，我们研究了整个妊娠期GDM中EV相关的miRNA谱，评估了它们在开发准确的多变量分类模型中的效用，并确定了骨骼肌蛋白质组中与EV miRNA谱变化相关的信号通路。发现：采用回顾性病例对照研究设计，以确定在妊娠和临床状态（即GDM或正常葡萄糖耐量，NGT）之间变化的EV相关miRNA。从妊娠早期、中期和晚期获得的母体血浆中分离EV（n = 29），并进行小RNA测序。通过实时PCR定量EV miRNA（病例= 8，对照= 14，在怀孕期间三次采样），并评估它们的单独和组合分类效率。定量，数据独立的采集质谱法被用来建立正常和GDM骨骼肌活检的蛋白质谱。使用小RNA文库分析了总共2822个miRNA，并且总共563个miRNA在整个妊娠期间显著变化（p < 0.05），并且101个miRNA在NGT和GDM之间显著变化。对NGT和GDM中miRNA变化的分析分别确定了总共256个（NGT组）和302个（GDM组）miRNA在整个妊娠期间发生变化。基于EV相关miRNA的定量表达，开发了多变量分类模型，并且正确分配样品的准确率> 90%。我们在GDM女性的骨骼肌活检中鉴定了一组与JAK-STAT信号相关的蛋白质，这些蛋白质可以被循环EV中的miRNA-92 a-3 p靶向。有趣的是，原代骨骼肌细胞中miRNA-92 a-3 p的过表达增加了胰岛素刺激的葡萄糖摄取。在妊娠早期，不同表达的EV相关miRNA可能在识别随后在妊娠后期发展为GDM的前驱妇女中具有临床实用性。我们认为EV中的miRNA-92 a-3 p可能是GDM中增加骨骼肌胰岛素敏感性的保护机制。在线版本包含补充材料，可通过10.1186/s12967-021-02999-9获得。
Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9–15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile. Discovery: A retrospective, case–control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM. A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake. During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM. The online version contains supplementary material available at 10.1186/s12967-021-02999-9.
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影响因子：
2.7
作者：
Cheng J;Morisaki H;Toyama K;Sugimoto N;Shintani T;Tandelilin A;Hirase T;Holmes EW;Morisaki T
通讯作者：
Morisaki T
影响因子：
5.1
作者：
Agarwal, Mukesh M.;Boulvain, Michel;Samad, Noorjahan
通讯作者：
Samad, Noorjahan
影响因子：
3.2
作者：
Cai M;Kolluru GK;Ahmed A
通讯作者：
Ahmed A
影响因子：
16.6
作者：
Chen Y;Buyel JJ;Hanssen MJ;Siegel F;Pan R;Naumann J;Schell M;van der Lans A;Schlein C;Froehlich H;Heeren J;Virtanen KA;van Marken Lichtenbelt W;Pfeifer A
通讯作者：
Pfeifer A
DOI：
10.1530/rep-10-0088
发表时间：
2010-09
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Catalano PM
通讯作者：
Catalano PM