Microvesicles-mediated communication between endothelial cells modulates,endothelial survival,and angiogenic function via transferring of miR-125a-5p |
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Authors: | Qunwen Pan Chunlian Ma Yan Wang Jinju Wang Jieyi Zheng Donghui Du Xiaorong Liao Yusen Chen Yanfang Chen Ji Bihl Can Chen Yi Yang Xiaotong Ma |
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Affiliation: | 1. Department of Guangdong Key Laboratory of Age Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;2. Department of Health Science, Wuhan Sports University, Wuhan, China;3. Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio;4. Department of Guangdong Key Laboratory of Age Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio |
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Abstract: | 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. |
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Keywords: | brain endothelial cells (ECs) cell function hypoxia and reperfusion microvesicles (MVs) miR-125a-5p |
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