Microvesicles-mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR-125a-5p
Microvesicles-mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR-125a-5p
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微泡介导的内皮细胞之间的通讯通过 miR-125a-5p 的转移调节内皮存活和血管生成功能
DOI：
10.1002/jcb.27581
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发表时间：
2019
影响因子：
4
通讯作者：
Ma Xiaotong
中科院分区：
文献类型：
--
作者：
Pan Qunwen;Ma Chunlian;Wang Yan;Wang Jinju;Zheng Jieyi;Du Donghui;Liao Xiaorong;Chen Yusen;Chen Yanfang;Bihl Ji;Chen Can;Yang Yi;Ma Xiaotong
内皮细胞（EC）释放的微囊泡（EMV）可通过转移其microRNA（miRs）来调节靶细胞的功能。我们已经报道了miR-125 a-5 p保护EC功能。在本研究中，我们确定EMV是否通过转移miR-125 a-5 p对EC产生有益影响。用miR-125 a-5 p模拟物或miR-125 a-5 p短发夹RNA转染人脑微血管EC，以获得miR-125 a-5 p过表达EC和miR-125 a-5 p敲低EC及其衍生的EMV。对于功能研究，将EC或缺氧/复氧损伤的EC与各种EMV共孵育。检测内皮细胞的存活率和血管生成功能。采用Western blot和定量真实的时间聚合酶链反应（qRT-PCR）测定磷酸肌醇3-激酶（PI 3 K）、磷酸化-Akt（p-Akt）/Akt、p-内皮型一氧化氮合酶（p-eNOS）、裂解型caspase-3和miR-125 a-5 p的水平。PI 3 K抑制剂用于通路分析。EMV可促进内皮细胞增殖、迁移和管腔形成能力，降低内皮细胞凋亡率。这些作用与p-Akt/Akt和p-eNOS增加相关，LY 294002可消除切割的caspase-3的减少。EMV中miR-125 a-5 p的过表达或下调促进或抑制EMV的这些作用。EMV可通过递送miR-125 a-5 p调节PI 3 K/Akt/eNOS通路和caspase-3的表达，增强EC的存活和血管生成功能。
Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR‐125a‐5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR‐125a‐5p. Human brain microvessel ECs were transfected with miR‐125a‐5p mimic or miR‐125a‐5p short hairpin RNA to obtain miR‐125a‐5p overexpressing ECs and miR‐125a‐5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT‐PCR) were used for measuring the levels of phosphoinositide 3‐kinase (PI3K), phosphorylation‐Akt (p‐Akt)/Akt, p‐endothelial nitric oxide synthase (p‐eNOS), cleaved caspase‐3, and miR‐125a‐5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p‐Akt/Akt and p‐eNOS, and a decrease in cleaved caspase‐3 could be abolished by LY294002. Overexpression or downregulation of miR‐125a‐5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR‐125a‐5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase‐3.