Department of Obstetrics and Gynecology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Diabetes. 2022 Nov 1;71(11):2272-2283. doi: 10.2337/db21-0909.
To date, the miRNA expression profile of plasma exosomes in women whose pregnancy is complicated by gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small-RNA sequencing in 12 pregnant women with GDM and 12 with normal glucose tolerance (NGT) and validated in 102 pregnant women with GDM and 101 with NGT. A total of 22 exosomal miRNAs were found, five of which were verified by real-time qPCR. Exosomal miR-423-5p was upregulated, whereas miR-122-5p, miR-148a-3p, miR-192-5p, and miR-99a-5p were downregulated in women whose pregnancy was complicated by GDM. IGF1R and GYS1 as target genes of miR-423-5p, and G6PC3 and FDFT1 as target genes of miR-122-5p were associated with insulin and AMPK signaling pathways and may participate in the regulation of metabolism in GDM. The five exosomal miRNAs had an area under the curve of 0.82 (95%CI, 0.73, ∼0.91) in early prediction of GDM. Our study demonstrates that dysregulated exosomal miRNAs in plasma from pregnant women with GDM might influence the insulin and AMPK signaling pathways and could contribute to the early prediction of GDM.
迄今为止，妊娠期糖尿病（GDM）孕妇血浆外泌体中的 miRNA 表达谱尚未完全阐明。在这项研究中，通过高通量小 RNA 测序鉴定了 12 名 GDM 孕妇和 12 名糖耐量正常（NGT）孕妇的血浆外泌体差异表达 miRNA，并在 102 名 GDM 孕妇和 101 名 NGT 孕妇中进行了验证。共发现 22 个外泌体 miRNA，其中 5 个通过实时 qPCR 验证。GDM 孕妇的血浆外泌体 miR-423-5p 上调，而 miR-122-5p、miR-148a-3p、miR-192-5p 和 miR-99a-5p 下调。IGF1R 和 GYS1 是 miR-423-5p 的靶基因，G6PC3 和 FDFT1 是 miR-122-5p 的靶基因，它们与胰岛素和 AMPK 信号通路相关，可能参与 GDM 的代谢调节。这 5 个外泌体 miRNA 在 GDM 的早期预测中 AUC 为 0.82（95%CI，0.73，∼0.91）。我们的研究表明，GDM 孕妇血浆外泌体中失调的 miRNA 可能影响胰岛素和 AMPK 信号通路，并有助于 GDM 的早期预测。
