Interferon-γ alters the immune-related miRNA expression of microvesicles derived from mesenchymal stem cells
Interferon-γ alters the immune-related miRNA expression of microvesicles derived from mesenchymal stem cells
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干扰素-γ 改变源自间充质干细胞的微泡的免疫相关 miRNA 表达。
DOI：
10.1007/s11596-017-1712-1
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发表时间：
2017-04-01
影响因子：
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通讯作者：
Wang，Hong-xiang
中科院分区：
文献类型：
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作者：
Zhao，Ai-qi;Xie，Hui;Wang，Hong-xiang
越来越多的研究表明，干扰素γ (IFN-γ)作为一种关键的炎症细胞因子，在诱导间充质干细胞（MSCs）的免疫抑制作用中是必不可少的。然而，IFN-γ刺激的MSCs （γMSCs）增强免疫抑制作用的机制尚不完全清楚。骨髓间充质干细胞衍生的微囊泡（msc - mv）被认为是骨髓间充质干细胞免疫抑制作用的潜在关键介质。此外，microRNAs （miRNAs）是免疫过程的重要调节因子，可以通过mv在细胞间穿梭。本研究旨在分析γ间充质干细胞衍生的MVs （γMSC-MVs）的miRNA表达特征，为进一步了解其亲本细胞的免疫抑制特性提供依据。通过miRNA芯片和生物信息学分析，我们在γ msc - mv中发现了62个与msc - mv显著表达差异的miRNA （DEMs）。并对dem调控的潜在靶基因和信号通路进行了预测和分析。有趣的是，许多dem和预测的信号通路已被证明参与免疫调节。进一步构建了免疫调节相关通路与相关dem之间的网络。总之，我们对γ间充质干细胞- mvs的miRNA谱的研究不仅为γ间充质干细胞增强免疫抑制特性的机制提供了新的视角，而且为这些强效细胞器的临床应用铺平了道路。
Increasing studies have demonstrated that interferon gamma (IFN-γ), which serves as a critical inflammatory cytokine, is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs). However, the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood. MSC-derived microvesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs. Moreover, microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs. The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs), which may provide better understanding of the immunosuppressive property of their parent cells. Through miRNA microarray and bioinformatics analysis, we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs. And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed. Interestingly, many DEMs and predicted signaling pathways had been demonstrated to be involved in immunoregulation. Furthermore, the network between immunoregulation-related pathways and relevant DEMs was constructed. Collectively, our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs, but also paves the way to clinical application of these potent organelles in the future.