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人脐带间充质基质细胞和细胞外囊泡的综合微小RNA分析

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

作者信息

Zou Xiang-Yu, Yu Yongjiang, Lin Sihao, Zhong Liang, Sun Jie, Zhang Guangyuan, Zhu Yingjian

机构信息

Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Kidney Blood Press Res. 2018;43(1):152-161. doi: 10.1159/000487369. Epub 2018 Feb 8.

Abstract

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.

摘要

背景/目的:间充质基质细胞(MSCs)参与许多不同器官的组织特异性修复,尤其是肾脏。它们的作用主要由包括细胞外囊泡(EVs)在内的因子的旁分泌释放介导,EVs由微囊泡和外泌体组成。EVs的相应微小RNA(miRNAs)被认为对其生物学功能很重要。

方法

从人脐带中培养MSCs,并从培养基中分离出EVs。通过微阵列分析确定MSCs和EVs中miRNAs的表达水平,并使用基因本体论(GO)分析其靶基因的功能。

结果

MSCs和EVs具有相似的miRNA表达谱,但有少数选择性富集的miRNAs除外。GO分析表明,与MSCs不同,富含EV的miRNAs的靶基因与钙通道调节和细胞连接活动相关,这可能表明MSCs和EVs具有不同的调节特性。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,富含EV的miRNAs靶向与氧化应激、T细胞活化和Toll样受体信号相关的基因。在MSCs和EVs中均富集的miRNAs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EVs具有相似的miRNA组成,在MSCs和EVs中观察到的一些选择性富集的miRNAs可能通过一些特定的信号通路影响不同的靶基因。

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