Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies.
Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies.
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DOI：
10.1371/journal.pone.0267564
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
我们进行了一项前瞻性的时间研究，收集了同意的孕妇的血液样本，以检验携带特定非编码microRNA签名的循环细胞外小泡(EV)可能是妊娠期糖尿病(GDM)的基础的假设。为了验证这一假设，分离的和具有特征的EV的miRNA货物揭示了胎盘的贡献以及在所有三个月和分娩时怀孕和非怀孕状态之间的差异表达。许多miRNAs起源于胎盘特异的19号染色体microRNA簇(19MC)和14号染色体microRNA簇(14MC)。此外，在正常妊娠组和妊娠期糖尿病组中，妊娠晚期和分娩时含有miRNA的EV与相应的产后胎盘表达的EV呈正相关(R值=0.63~0.69，p=2.2X10-16)。此外，在所有三个月中，后来患上妊娠期糖尿病的妇女之间出现了明显的差异。Logistic回归和留一法交叉验证分析显示，在妊娠期糖尿病早期，使用所有循环miRNAs(miR-92a-3p、miR-192-5p、miR-451a、miR-122-5p)或仅使用差异表达的miRNAs(has-miR-92a-3p、hsa-miR-92b-3p、hsa-miR-100-5p和hsa-miR-125a-3p)的miRNAs的最佳组合。作为第一步，两组miRNAs都显示出了预测概率，其面积在0.95到0.96之间。这些miRNAs针对与细胞新陈代谢、增殖和免疫耐受有关的基因。特别是P-I-3-Kinase、FOXO、胰岛素信号通路和生糖通路的基因被作为靶点，提示胎盘与各种母体器官/细胞的连接，改变了生理以及随后发生GDM的致病机制。我们得出的结论是，来自胎盘的循环EV及其miRNA货物在母体器官中沟通和调节信号通路，从而预先决定GDM的发展。
We undertook a prospective temporal study collecting blood samples from consenting pregnant women, to test the hypothesis that circulating extracellular vesicles (EVs) carrying specific non-coding microRNA signatures can underlie gestational diabetes mellitus (GDM). To test this hypothesis, miRNA cargo of isolated and characterized EVs revealed contributions from the placenta and differential expression at all three trimesters and at delivery between pregnant and non-pregnant states. Many miRNAs originate from the placental-specific chromosome 19 microRNA cluster (19MC) and chromosome 14 microRNA cluster (14MC). Further a positive correlation emerged between third trimester and at delivery EVs containing miRNAs and those expressed by the corresponding post-parturient placentas (R value = 0.63 to 0.69, p value = 2.2X10-16), in normal and GDM. In addition, distinct differences at all trimesters emerged between women who subsequently developed GDM. Analysis by logistic regression with leave-one-out-cross validation revealed the optimal combination of miRNAs using all the circulating miRNAs (miR-92a-3p, miR-192-5p, miR-451a, miR-122-5p), or using only the differentially expressed miRNAs (has-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-100-5p and hsa-miR-125a-3p) in GDM during the first trimester. As an initial step, both sets of miRNAs demonstrated a predictive probability with an area under the curve of 0.95 to 0.96. These miRNAs targeted genes involved in cell metabolism, proliferation and immune tolerance. In particular genes of the P-I-3-Kinase, FOXO, insulin signaling and glucogenic pathways were targeted, suggestive of placental connectivity with various maternal organs/cells, altering physiology along with pathogenic mechanisms underlying the subsequent development of GDM. We conclude that circulating EVs originating from the placenta with their miRNA cargo communicate and regulate signaling pathways in maternal organs, thereby predetermining development of GDM.
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影响因子：
7.4
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
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Salomon C
影响因子：
2.7
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Herrera BM;Lockstone HE;Taylor JM;Wills QF;Kaisaki PJ;Barrett A;Camps C;Fernandez C;Ragoussis J;Gauguier D;McCarthy MI;Lindgren CM
通讯作者：
Lindgren CM
影响因子：
3.8
作者：
Morales-Prieto, D. M.;Chaiwangyen, W.;Markert, U. R.
通讯作者：
Markert, U. R.
影响因子：
3.8
作者：
Janzen, C.;Lei, M. Y. Y.;Cho, J.;Sullivan, P.;Shin, B. -C.;Devaskar, S. U.
通讯作者：
Devaskar, S. U.
影响因子：
8.3
作者：
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Sadovsky, Yoel