Zhao Ai-Qi, Xie Hui, Lin Sheng-Yan, Lei Qian, Ren Wen-Xiang, Gao Fei, Guo Hao, Guo An-Yuan, Chen Zhi-Chao, Wang Hong-Xiang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2017 Apr;37(2):179-184. doi: 10.1007/s11596-017-1712-1. Epub 2017 Apr 11.
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.
越来越多的研究表明，作为一种关键炎性细胞因子的干扰素γ（IFN-γ），对于诱导间充质干细胞（MSC）的免疫抑制作用至关重要。然而，IFN-γ刺激的MSC（γMSC）增强免疫抑制作用的潜在机制尚未完全阐明。MSC衍生的微泡（MSC-MV）被视为MSC免疫抑制作用的潜在关键介质。此外，微小RNA（miRNA）是免疫过程的重要调节因子，并且可以通过MV在细胞间穿梭。我们研究的目的是分析γMSC衍生的MV（γMSC-MV）的miRNA表达特征，这可能有助于更好地理解其亲代细胞的免疫抑制特性。通过miRNA微阵列和生物信息学分析，我们发现与MSC-MV相比，γMSC-MV中有62个显著差异表达的miRNA（DEM）。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。此外，构建了免疫调节相关通路与相关DEM之间的网络。总的来说，我们对γMSC-MV的miRNA库的研究不仅为γMSC增强免疫抑制特性的潜在机制提供了新的视角，也为这些强大细胞器未来的临床应用铺平了道路。
