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人脐带间充质干细胞来源的外泌体介导的 microRNA-133b 转移通过限制 SGK1 促进子痫前期滋养细胞的增殖、迁移和侵袭。

Human umbilical cord mesenchymal stem cell-derived exosome-mediated transfer of microRNA-133b boosts trophoblast cell proliferation, migration and invasion in preeclampsia by restricting SGK1.

机构信息

Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University , Shengyang, Liaoning, China.

出版信息

Cell Cycle. 2020 Aug;19(15):1869-1883. doi: 10.1080/15384101.2020.1769394. Epub 2020 Jun 28.

Abstract

OBJECTIVE

Exosomes have been documented to function in human diseases, yet their transfer of microRNA (miRNA) in preeclampsia (PE) has seldom been reported. This study intends to discuss the role of miR-133b derived from exosomes in human umbilical cord mesenchymal stem cells (hUC-MSCs) in trophoblast cell development in PE.

METHODS

Placentas from PE patients and normal pregnant women were collected. The hUC-MSCs and their exosomes were obtained and identified. Trophoblast cell HPT-8 and HTR8-S/Vneo were obtained and co-cultured with hUC-MSCs-derived exosomes that had been transfected with different miR-133b plasmids. MiR-133b and glucocorticoid-regulated kinase 1 (SGK1) expression in placental tissues and HPT-8 and HTR8-S/Vneo cells was determined. HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle distribution, apoptosis rate, migration and invasion were detected.

RESULTS

MiR-133b was down-regulated and SGK1 was up-regulated in placental tissues of PE patients. MiR-133b expression was inversely related to SGK1 expression in HTR8-S/Vneo and HPT-8 cells co-cultured with hUC-MSC-derived exosomes. Exosomes promoted HTR8-S/Vneo and HPT-8 cell proliferation, migration and invasion abilities, cell cycle entry and inhibited apoptosis. Elevated exosome-derived miR-133b from hUC-MSCs boosted HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle progression, migration and invasion and limited cell apoptosis. MiR-133b targeted SGK1.

CONCLUSION

Collectively, we demonstrate that miR-133b is down-regulated and SGK1 is up-regulated in PE, and miR-133b derived from exosomes in hUM-MSCs facilitates trophoblast cell proliferation, migration and invasion in PE via constraining SGK1.

摘要

目的

已有研究证实外泌体在人类疾病中发挥作用,但关于其在子痫前期(PE)中微小 RNA(miRNA)转移的报道甚少。本研究旨在探讨来源于人脐带间充质干细胞(hUC-MSCs)外泌体的 miR-133b 在 PE 中滋养细胞发育中的作用。

方法

收集 PE 患者和正常孕妇的胎盘。获取并鉴定 hUC-MSCs 及其外泌体。获得滋养细胞 HPT-8 和 HTR8-S/Vneo,并与转染了不同 miR-133b 质粒的 hUC-MSCs 衍生外泌体共培养。检测胎盘组织和 HPT-8、HTR8-S/Vneo 细胞中 miR-133b 和糖皮质激素调节激酶 1(SGK1)的表达。检测 HTR8-S/Vneo 和 HPT-8 细胞的增殖、细胞周期分布、凋亡率、迁移和侵袭能力。

结果

PE 患者胎盘组织中 miR-133b 下调,SGK1 上调。与 hUC-MSC 衍生外泌体共培养的 HTR8-S/Vneo 和 HPT-8 细胞中,miR-133b 的表达与 SGK1 的表达呈负相关。外泌体促进 HTR8-S/Vneo 和 HPT-8 细胞的增殖、迁移和侵袭能力,促进细胞周期进入,抑制细胞凋亡。hUC-MSCs 来源的外泌体中 miR-133b 水平升高促进了 HTR8-S/Vneo 和 HPT-8 细胞的增殖、细胞周期进程、迁移和侵袭,限制了细胞凋亡。miR-133b 靶向 SGK1。

结论

综上所述,我们证实 miR-133b 在 PE 中下调,SGK1 上调,hUC-MSCs 来源的外泌体 miR-133b 通过抑制 SGK1 促进 PE 中滋养细胞的增殖、迁移和侵袭。

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