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.

中文翻译：

---

人脐带间充质干细胞衍生的外泌体介导的 microRNA-133b 转移通过限制 SGK1 促进先兆子痫中的滋养层细胞增殖、迁移和侵袭。

客观的

外泌体已被证明在人类疾病中起作用，但很少报道它们在先兆子痫 (PE) 中转移 microRNA (miRNA)。本研究旨在探讨人脐带间充质干细胞 (hUC-MSCs) 外泌体来源的 miR-133b 在 PE 滋养层细胞发育中的作用。

方法

收集PE患者和正常孕妇的胎盘。获得并鉴定了 hUC-MSCs 及其外泌体。获得滋养层细胞 HPT-8 和 HTR8-S/Vneo，并与转染不同 miR-133b 质粒的 hUC-MSCs 来源的外泌体共培养。测定了胎盘组织和 HPT-8 和 HTR8-S/Vneo 细胞中的 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细胞增殖、细胞周期分布、凋亡率、迁移和侵袭。

结果

在 PE 患者的胎盘组织中，miR-133b 下调，SGK1 上调。在与 hUC-MSC 衍生的外泌体共培养的 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 细胞增殖、迁移和侵袭能力，进入细胞周期并抑制细胞凋亡。来自 hUC-MSC 的外泌体来源的 miR-133b 升高，可促进 HTR8-S/Vneo 和 HPT-8 细胞增殖、细胞周期进程、迁移和侵袭，并限制细胞凋亡。MiR-133b 靶向 SGK1。

结论

总的来说，我们证明 miR-133b 在 PE 中下调而 SGK1 上调，来自 hUM-MSCs 外泌体的 miR-133b 通过抑制 SGK1 促进 PE 中的滋养层细胞增殖、迁移和侵袭。