Zubkova Ekaterina, Evtushenko Evgeniy, Beloglazova Irina, Osmak German, Koshkin Phillip, Moschenko Alexander, Menshikov Mikhail, Parfyonova Yelena
Federal State Budgetary Institution (FSBI), "National Medical Research Center of Cardiology," Ministry of Health of the Russian Federation, Moscow, Russia.
Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Front Cell Dev Biol. 2021 Nov 15;9:754025. doi: 10.3389/fcell.2021.754025. eCollection 2021.
Mesenchymal stem/stromal cells (MSCs) represent a promising tool to treat cardiovascular diseases. One mode of action through which MSCs exert their protective effects is secretion of extracellular vesicles (EVs). Recently, we demonstrated that rat adipose-derived MSC-overexpressing stem cell factor (SCF) can induce endogenous regenerative processes and improve cardiac function. In the present work, we isolated EVs from intact, GFP- or SCF-overexpressing rat MSC and analyzed microarray datasets of their miRNA cargo. We uncovered a total of 95 differentially expressed miRNAs. We did not observe significant differences between EVs from GFP-MSC and SCF-MSC that may indicate intrinsic changes in MSC after viral transduction. About 80 miRNAs were downregulated in EVs from both SCF- or GFP-MSC. We assembled the miRNA-based network and found several nodes of target genes among which Vim Sept3 and Vsnl1 are involved in regulation of cellular migration that is consistent with our previous EVs data. Topological analyses of the network also revealed that among the downregulated miRNA-rno-miRNA-128-3p that regulates plenty of targets is presumably associated with chemokine signaling pathways. Overall, our data suggest that genetic modification of MSC has a great impact on their miRNA composition and provide novel insights into the regulatory networks underlying EV effects.
间充质干/基质细胞（MSCs）是治疗心血管疾病的一种有前景的工具。MSCs发挥其保护作用的一种作用方式是分泌细胞外囊泡（EVs）。最近，我们证明过表达干细胞因子（SCF）的大鼠脂肪来源的MSCs能够诱导内源性再生过程并改善心脏功能。在本研究中，我们从完整的、过表达绿色荧光蛋白（GFP）或SCF的大鼠MSCs中分离出EVs，并分析了其miRNA货物的微阵列数据集。我们共发现95种差异表达的miRNA。我们未观察到来自GFP-MSCs和SCF-MSCs的EVs之间存在显著差异，这可能表明病毒转导后MSCs的内在变化。来自SCF-或GFP-MSCs的EVs中约80种miRNA表达下调。我们构建了基于miRNA的网络，并发现了几个靶基因节点，其中波形蛋白Sept3和Vsnl1参与细胞迁移的调控，这与我们之前的EVs数据一致。对该网络的拓扑分析还显示，在下调的miRNA-rno-miRNA-128-3p中，其调控大量靶标，可能与趋化因子信号通路有关。总体而言，我们的数据表明MSCs的基因修饰对其miRNA组成有很大影响，并为EVs效应背后的调控网络提供了新的见解。
