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外泌体miR-137-3p靶向泛素蛋白连接酶E3C以激活信号转导和转录激活因子3,促进人脐带间充质干细胞在缺氧条件下向内膜上皮细胞迁移和分化。

Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia.

作者信息

Zhang Wan-Yu, Liu Si-Miao, Wang Han-Bi, Deng Cheng-Yan

机构信息

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing 100730, China.

出版信息

World J Stem Cells. 2025 Apr 26;17(4):100359. doi: 10.4252/wjsc.v17.i4.100359.

Abstract

BACKGROUND

Thin endometrium, leading cause of recurrent implantation failure and infertility, has been found to respond to exosomes.

AIM

To investigate the efficacy of exosomes in addressing the issue of thin endometrium.

METHODS

RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs (miRNAs) in human umbilical cord mesenchymal stem cell (hucMSC) treated with exosomes enriched with endometrial cell-derived components. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways, molecular functions, and cellular components. Transwell and wound healing assays were performed to assess migratory potential, and western blotting was detected protein level.

RESULTS

A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components, comprising 27 upregulated and 26 downregulated miRNAs, which includes miR-137-3p. Enhanced migratory potential was observed in the Transwell and wound healing assays, and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3. These effects were attributed to the upregulation of miR-137-3p.

CONCLUSION

miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway, enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.

摘要

背景

薄型子宫内膜是反复种植失败和不孕的主要原因,已发现其对外泌体有反应。

目的

探讨外泌体在解决薄型子宫内膜问题方面的疗效。

方法

采用RNA测序和逆转录定量聚合酶链反应,鉴定用富含子宫内膜细胞衍生成分的外泌体处理的人脐带间充质干细胞(hucMSC)中差异表达的微小RNA(miRNA)。此外,进行基因本体论和京都基因与基因组百科全书分析,以突出特定生物途径、分子功能和细胞成分中的显著富集。进行Transwell和伤口愈合试验以评估迁移潜力,并通过蛋白质印迹法检测蛋白质水平。

结果

在用富含子宫内膜细胞衍生成分的外泌体处理的hucMSC中,共鉴定出53种差异表达的miRNA,包括27种上调的miRNA和26种下调的miRNA,其中包括miR-137-3p。在Transwell和伤口愈合试验中观察到迁移潜力增强,蛋白质印迹法证实了hucMSC的上皮分化以及磷酸化信号转导和转录激活因子3的增加。这些作用归因于miR-137-3p的上调。

结论

缺氧影响的子宫内膜上皮细胞来源的外泌体中的miR-137-3p刺激信号转导和转录激活因子3信号通路,增强hucMSC向子宫内膜上皮细胞的迁移和分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98c6/12038465/47a48bea60d4/100359-g001.jpg

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