Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu
Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu
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外泌体 miR-423-5p 通过靶向 Sufu 介导人脂肪干细胞的促血管生成活性
DOI：
10.1186/s13287-019-1196-y
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发表时间：
2019-03
影响因子：
7.5
通讯作者：
Zhou Zhou
中科院分区：
文献类型：
--
作者：
Fen Xu;Qinqin Xiang;Jiuzuo Huang;Qianlong Chen;Xiaojun Wang;Xiao Long;Zhou Zhou
背景人脂肪干细胞（hADSCs）是再生医学的重要细胞来源。与周围微环境广泛相互作用的证据使研究人员更多地关注hADSC作为再生途径的激活剂，而不是简单地替换受损细胞。一些研究发现，功能性miRNA可以包装到外泌体中，并从供体细胞转移到受体细胞中，这表明转运的miRNA可能是一类新的细胞到细胞的调节物种。本研究的目的是评估hADSCs分泌的外泌体衍生的miRNA是否能够影响血管生成，组织regeneration.MethodsExosomes的关键步骤，从hADSCs纯化，然后通过表征其表型和血管生成潜力在体外。进行RNA测序以检测在hADSC衍生的外泌体中富集的miRNA。A miRNA模拟实验被用来检测的hADSC衍生的exosomes.ResultsExosomes的proangiogenic活性的关键miRNA的特征在于从hADSC分离的圆形膜囊泡的大小约为100 nm，是积极的CD 9和flotillin。外泌体被原代人脐静脉内皮细胞（HUVEC）内化并刺激HUVEC增殖和迁移。值得注意的是，外泌体以剂量依赖性方式促进HUVEC的血管样形成，其最大活性（10 μg/mL）与5%FBS相当。RNA-seq生物信息学分析预测了基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路分析中前30位exosomal miRNAs的1119个基因靶点，参与血管生成的通路是KEGG通路中的前30位。结论Exosomal miR-423 - 5 p通过靶向Sufu介导hADSCs的促血管生成活性，这可能有助于开发hADSCs exosomes作为再生医学的治疗工具。
BackgroundHuman adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration.MethodsExosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes.ResultsExosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 μg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu.ConclusionsExosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine.
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