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首页> 外文期刊>Biology Open >Exosomal transfer of bone marrow mesenchymal stem cell-derived miR-340 attenuates endometrial fibrosis
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Exosomal transfer of bone marrow mesenchymal stem cell-derived miR-340 attenuates endometrial fibrosis

机译：骨髓间充质干细胞来源的miR-340的外体转移可减轻子宫内膜纤维化

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Bone marrow mesenchymal stem cells (BMSCs) have potential therapeutic benefits for the treatment of endometrial diseases and injury. BMSCs interact with uterus parenchymal cells by direct contact or indirect secretion of growth factors to promote functional recovery. In this study, we found that BMSC treatment in rats subjected to mechanical damage (MD) significantly increased microRNA-340 (miR-340) levels in the regenerated endometrium. Then we employed knockin and knockdown technologies to upregulate or downregulate the miR-340 level in BMSCs (miR-340+BMSCs or miR-340?BMSCs) and their corresponding exosomes, respectively, to test whether exosomes from BMSCs mediate miR-340 transfer. We found that the exosomes released from the primitive BMSCs or miR-340+BMSCs but not miR-340?BMSCs increased the miR-340 levels in primary cultured endometrial stromal cells (ESCs) compared with control. Further verification of this exosome-mediated intercellular communication was performed using exosomal inhibitor GW4869. Tagging exosomes with red fluorescent protein demonstrated that exosomes were released from BMSCs and transferred to adjacent ESCs. Compared with controls, rats receiving primitive BMSC treatment significantly improved functional recovery and downregulated collagen 1α1, α-SMA and transforming growth factor (TGF)-β1 at day 14 after MD. The outcomes were significantly enhanced by miR-340+BMSC treatment, and were significantly weakened by miR-340?BMSC treatment, compared with primitive BMSC treatment.In vitrostudies reveal that miR-340 transferred from BMSCs suppresses the upregulated expression of fibrotic genes in ESCs induced by TGF-β1. These data suggest that the effective antifibrotic function of BMSCs is able to transfer miR-340 to ESCs by exosomes, and that enhancing the transfer of BMSC-derived miR-340 is an alternative modality in preventing intrauterine adhesion.
机译：骨髓间充质干细胞（BMSC）具有治疗子宫内膜疾病和损伤的潜在治疗优势。 BMSC通过直接接触或间接分泌生长因子来促进功能恢复，从而与子宫实质细胞相互作用。在这项研究中，我们发现在遭受机械损伤（MD）的大鼠中进行BMSC治疗可显着提高再生子宫内膜中的microRNA-340（miR-340）水平。然后我们采用敲入和敲低技术分别上调或下调BMSCs（miR-340 + BMSCs或miR-340？BMSCs）及其相应的外泌体中的miR-340水平，以测试BMSCs的外泌体是否介导miR-340的转移。我们发现，与对照相比，从原始BMSC或miR-340 + BMSC释放的外泌体而不是miR-340？BMSC释放的外泌体增加了原代培养的子宫内膜基质细胞（ESC）中的miR-340水平。使用外泌体抑制剂GW4869对这种外泌体介导的细胞间通讯进行了进一步验证。用红色荧光蛋白标记外泌体表明外泌体已从BMSC中释放出来并转移到相邻的ESC中。与对照组相比，接受原始BMSC治疗的大鼠在MD后第14天显着改善了功能恢复并下调了胶原1α1，α-SMA和转化生长因子（TGF）-β1。与原始BMSC处理相比，miR-340 + BMSC处理显着增强了结局，而miR-340？BMSC处理显着减弱了结局。体外研究表明，从BMSC转移的miR-340抑制了ESC中纤维化基因表达的上调。由TGF-β1诱导。这些数据表明，BMSC的有效抗纤维化功能能够通过外泌体将miR-340转移至ESC，并且增强BMSC衍生的miR-340的转移是预防子宫内粘连的另一种方式。

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