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 ...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,micro RNAs（miR NAs） 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 mi RNA expression signature of MVs derived from γMSCs（γMSC-MVs）,which may provide better understanding of the immunosuppressive property of their parent cells.Through mi RNA microarray and bioinformatics analysis,we found 62 significantly differentially expressed miR NAs（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 mi RNA 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.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81470330)Application Fundamental Research Project of Wuhan Science and Technology Bureau(No.2015061701011623)
文摘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,micro RNAs（miR NAs） 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 mi RNA expression signature of MVs derived from γMSCs（γMSC-MVs）,which may provide better understanding of the immunosuppressive property of their parent cells.Through mi RNA microarray and bioinformatics analysis,we found 62 significantly differentially expressed miR NAs（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 mi RNA 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.
