Comprehensive miRNA Analysis of Human Umbilical Cord-Derived Mesenchymal Stromal Cells and Extracellular Vesicles

Comprehensive miRNA Analysis of Human Umbilical Cord-Derived Mesenchymal Stromal Cells and Extracellular Vesicles
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DOI:
10.1159/000487369
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发表时间:
2018-02
影响因子:
2.8
通讯作者:
X. Zou;Yongjiang Yu;Sihao Lin;Liang Zhong;Jie Sun;Guangyuan Zhang;Yingjian Zhu
X. Zou;Yongjiang Yu;Sihao Lin;Liang Zhong;Jie Sun;Guangyuan Zhang;Yingjian Zhu
中科院分区:
医学4区
文献类型:
--
作者:
X. Zou;Yongjiang Yu;Sihao Lin;Liang Zhong;Jie Sun;Guangyuan Zhang;Yingjian Zhu

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背景/目的:间充质间质细胞(MSCs)参与许多不同器官的组织特异性修复,尤其是肾脏。它们的作用主要是由旁分泌释放的因子介导的,包括细胞外囊泡(EVs),它由微囊泡和外泌体组成。电动汽车相应的microrna (miRNAs)被认为对其生物学功能很重要。方法:从人脐带培养间充质干细胞,从培养基中分离出ev。通过微阵列分析确定MSCs和ev中mirna的表达水平,并使用基因本体(GO)分析其靶基因的功能。结果:除了少量选择性富集的miRNA外,MSCs和ev具有相似的miRNA表达谱。GO分析表明,与MSCs不同,ev富集mirna的靶基因与钙通道调控和细胞连接活性相关,这可能表明MSC和ev具有不同的调控特性。研究人员还分析了与肾损伤修复相关的血管生成、氧化应激和炎症信号通路,并发现ev富集的mirna靶向与氧化应激、T细胞活化和toll样受体信号传导相关的基因。在MSCs和ev中富集的mirna靶向调节血管生成和趋化因子释放的信号通路中的不同基因。结论:MSCs及其ev具有相似的miRNA成分,在MSCs和ev中观察到的一些选择性富集的miRNA可能通过一些特定的信号通路影响不同的靶基因。
Background/Aims: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. Methods: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium. The expression levels of miRNAs in MSCs and EVs were determined by microarray analysis, and gene ontology (GO) was used to analyze the functions of their target genes. Results: MSCs and EVs had similar miRNA expression profiles, with the exception of a small number of selectively enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV-enriched miRNAs were associated with calcium channel regulation and cell junction activities, which may indicate that MSC and EVs have different regulatory properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways related to the repair of renal injury were also analyzed, and EV-enriched miRNAs targeted genes associated with oxidative stress, T cell activation, and Toll-like receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different genes in signaling pathways regulating angiogenesis and chemokine release. Conclusion: MSCs and their EVs shared similar miRNA component, and some selectively enriched miRNAs observed in MSCs and EVs may affect different target genes through some specific signaling pathways.