Exosomes from bone mesenchymal stem cells alleviate mifepristone-induced human endometrial stromal cell injury by inhibiting TLR3 via delivering miR-941.

IF 2.2 4区医学 Q3 PHYSIOLOGY

Physiology international Pub Date : 2022-12-14 DOI:10.1556/2060.2022.00108

Yu Wang, Xiaofei Sun, Qing Yang, Lili Yin

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引用次数: 1

Abstract

Objective: We aim to investigate the protective effect and underlying mechanisms of BMSCs-exo on human endometrial stromal cells (HESCs) induced by mifepristone in this study.

Methods: BMSCs-exo were extracted and then identified by transmission electron microscopy and western-blot assay. RT-PCR assay was used to determine the level of miR-941. MiR-941 mimics or inhibitor were transfected into BMSCs and the exosomes were extracted. Then, Cell activity, apoptosis rate, cell migration and invasion, as well as the expression of angiogenic proteins were determined in HESCs stimulated by mifepristone and BMSCs-exo. Next, Dual-luciferase reporting assay was used to verify the targeted binding of miR-941 to TLR3, and the TLR3 expression in HESCs was detected by RT-PCR and western-blot. Finally, TLR3 was overexpressed to evaluate the effects of miR-941 from BMSCs-exo on cell apoptosis, cell invasion and angiogenesis in HESCs induced by mifepristone.

Results: miR-941 was highly expressed in BMSCs-exo. Exosome miR-941 in BMSCs-exo inhibited the cell apoptosis, and promoted cell activity, cell migration, invasion as well as angiogenesis were also improved in HESCs induced by mifepristone. TLR3 was a target of miR-941, which was up-regulated in mifepristonetreated HESCs. We further found that miR-941 derived from BMSCs-exo down-regulated the expression of TLR3 in HESCs treated by mifepristone. In addition, TLR3 overexpression blocked the inhibition of miR-941 on mifepristone-induced cell apoptosis, as well as cell migration and angiogenesis in HESCs.

Conclusions: Thus, we concluded that BMSCs-exo has protective effect on mifepristone-induced cell damage by delivering miR-941 which targeted TLR3 and regulated cell activity, migration, and angiogenesis in HESCs.

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骨间充质干细胞外泌体通过递送miR-941抑制TLR3，减轻米非司酮诱导的人子宫内膜基质细胞损伤。

目的:研究BMSCs-exo对米非司酮诱导的人子宫内膜基质细胞(HESCs)的保护作用及其机制。方法:提取BMSCs-exo，采用透射电镜和western-blot方法进行鉴定。RT-PCR检测miR-941水平。将MiR-941模拟物或抑制剂转染到骨髓间充质干细胞中，提取外泌体。在米非司酮和BMSCs-exo刺激的HESCs中，检测细胞活性、凋亡率、细胞迁移和侵袭以及血管生成蛋白的表达。接下来，采用双荧光素酶报告法验证miR-941与TLR3的靶向结合，并采用RT-PCR和western-blot检测HESCs中TLR3的表达。最后，我们过表达TLR3来评估BMSCs-exo中miR-941对米非司酮诱导HESCs细胞凋亡、细胞侵袭和血管生成的影响。结果:miR-941在BMSCs-exo中高表达。在米非司酮诱导的HESCs中，BMSCs-exo中的外泌体miR-941抑制了细胞凋亡，促进了细胞活性、细胞迁移、侵袭和血管生成。TLR3是miR-941的靶标，miR-941在米非司酮处理的HESCs中上调。我们进一步发现，来源于BMSCs-exo的miR-941下调了米非司酮处理HESCs中TLR3的表达。此外，TLR3过表达阻断了miR-941对米非司酮诱导的HESCs细胞凋亡、细胞迁移和血管生成的抑制作用。因此，我们得出结论，BMSCs-exo通过传递靶向TLR3的miR-941，在HESCs中调节细胞活性、迁移和血管生成，对米非司酮诱导的细胞损伤具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Physiology international Medicine-Physiology (medical)

CiteScore

3.40

自引率

0.00%

发文量

期刊介绍： The journal provides a forum for important new research papers written by eminent scientists on experimental medical sciences. Papers reporting on both original work and review articles in the fields of basic and clinical physiology, pathophysiology (from the subcellular organization level up to the oranizmic one), as well as related disciplines, including history of physiological sciences, are accepted.