Placenta-associated serum exosomal miR-155 derived from patients with preeclampsia inhibits eNOS expression in human umbilical vein endothelial cells
Placenta-associated serum exosomal miR-155 derived from patients with preeclampsia inhibits eNOS expression in human umbilical vein endothelial cells
复制标题
来自先兆子痫患者的胎盘相关血清外泌体 miR 155 抑制人脐静脉内皮细胞中的 eNOS 表达。
DOI：
10.3892/ijmm.2018.3367
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发表时间：
2018-03-01
影响因子：
5.4
通讯作者：
Hu, Yali
中科院分区：
文献类型：
--
作者：
Shen, Li;Li, Yujing;Hu, Yali
先兆子痫（PE）被认为是由妊娠早期胎盘形成异常引起的，并导致妊娠中期或晚期全身性内皮细胞功能障碍。人胎盘中表达的微小RNA（miRs）可以通过外泌体分泌到母体循环中，外泌体是分泌的细胞外囊泡，在细胞间通讯中起重要作用。本研究假设PE患者胎盘相关血清外泌体miR-155的上调可能抑制内皮细胞中内皮型一氧化氮合酶（eNOS）的表达。结果表明，来自PE患者的胎盘相关血清外泌体降低了原代人脐静脉内皮细胞（HUVEC）中一氧化氮（NO）的产生和eNOS的表达。随后，与胎龄匹配的正常孕妇相比，在PE患者中检测到胎盘相关血清外泌体miR-155的上调。此外，结果表明，来自BeWo细胞的外泌体miR-155的过表达被内化到HUVECs中，并且能够通过靶向其3 '-非翻译区来抑制eNOS表达。本研究的结果表明，胎盘相关的血清外泌体可能会抑制内皮细胞中eNOS的表达在人类PE的发展，这一现象可能是部分由于胎盘相关的血清外泌体中的miR-155表达增加。
Preeclampsia (PE) is considered to be initiated by abnormal placentation in early pregnancy and results in systemic endothelial cell dysfunction in the second or third trimester. MicroRNAs (miRs) expressed in the human placenta can be secreted into maternal circulation via exosomes, which are secreted extracellular vesicles that serve important roles in intercellular communication. The present study hypothesized that upregulation of placenta-associated serum exosomal miR-155 from patients with PE may suppress endothelial nitric oxide synthase (eNOS) expression in endothelial cells. The results demonstrated that placenta-associated serum exosomes from patients with PE decreased nitric oxide (NO) production and eNOS expression in primary human umbilical vein endothelial cells (HUVECs). Subsequently, an upregulation of placenta-associated serum exosomal miR-155 was detected in patients with PE compared with in gestational age-matched normal pregnant women. In addition, the results demonstrated that overexpression of exosomal miR-155 from BeWo cells was internalized into HUVECs, and was able to suppress eNOS expression by targeting its 3'-untranslated region. The results of the present study indicated that placenta-associated serum exosomes may inhibit eNOS expression in endothelial cell during PE development in humans, and this phenomenon may be partly due to increased miR-155 expression in placenta-associated serum exosomes.