Guangzhou Key Laboratory of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Int J Mol Sci. 2022 Oct 15;23(20):12343. doi: 10.3390/ijms232012343.
Myometrial contraction is essential for successful delivery. Recent studies have highlighted the vital roles of tissue-derived exosomes in disease diagnostic, prognostic, and therapeutic applications; however, the characteristics of uterine myometrium-derived exosomes are unclear. Here, we successfully isolated exosomes from myometrial tissues, human myometrial smooth muscle cells (HMSMCs), and human umbilical vein endothelial cells (HUVECs), then performed quantitative liquid chromatography-tandem mass spectrometry and miRNA sequencing to investigate the cargo of the exosomes. Fifty-two proteins and five miRNAs were differentially expressed (DE) in term non-labor and term labor myometrium-derived exosomes. Among them, seven proteins (SERPINE1, THBS1, MGAT1, VIM, FGB, FGG, and VWF) were differentially expressed both in the myometrial exosomes and tissues, three miRNAs (miR-363-3p, miR-203a-3p, and miR-205-5p) target 13 DE genes. The top three miRNA derived from HMSMCs (miR-125b-1-3p, miR-337-5p, and miR-503-5p) and HUVECs (miR-663a, miR-4463, and miR-3622a-5p) were identified. Two proteins, GJA1 and SLC39A14, exist in female blood exosomes and are highly expressed in HMSMCs exosomes, are also upregulated in the laboring myometrium, which verified increased in laboring blood samples, might be novel potential biomarkers for myometrial activation. The proteomic and miRNA profile of exosomes derived from laboring myometrium revealed some molecules in the exosomes that affect the intercellular communication and the function of the myometrium.
子宫肌层收缩对于成功分娩至关重要。最近的研究强调了组织衍生的外泌体在疾病诊断、预后和治疗应用中的重要作用；然而，子宫肌层来源的外泌体的特征尚不清楚。在这里，我们成功地从肌层组织、人子宫平滑肌细胞（HMSMC）和人脐静脉内皮细胞（HUVEC）中分离出外泌体，然后进行定量液相色谱-串联质谱和 miRNA 测序，以研究外泌体的货物。在足月未分娩和足月分娩的肌层来源的外泌体中，有 52 种蛋白质和 5 种 miRNA 表达差异（DE）。其中，7 种蛋白质（SERPINE1、THBS1、MGAT1、VIM、FGB、FGG 和 VWF）在肌层外泌体和组织中均有差异表达，3 种 miRNA（miR-363-3p、miR-203a-3p 和 miR-205-5p）靶向 13 个 DE 基因。来源于 HMSMC 的前 3 种 miRNA（miR-125b-1-3p、miR-337-5p 和 miR-503-5p）和 HUVEC 的（miR-663a、miR-4463 和 miR-3622a-5p）被鉴定出来。两种蛋白质，GJA1 和 SLC39A14，存在于女性血液外泌体中，在 HMSMC 外泌体中高度表达，在分娩肌层中也上调，这在分娩血液样本中得到了验证，可能是肌层激活的新的潜在生物标志物。来源于分娩肌层的外泌体的蛋白质组学和 miRNA 图谱揭示了外泌体中一些影响细胞间通讯和肌层功能的分子。
