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Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis

机译:脂肪来源的间充质干细胞来源的外来体介导的microRNA-342-5p保护内皮细胞免于动脉粥样硬化

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摘要

Exosomes are reported to mediate several disease-related microRNAs (miRNAs) to affect the progression of diseases, including atherosclerosis. Here, we aimed to screen the atherosclerosis-associated miRNAs and preliminarily investigate the potential regulatory mechanism of atherosclerosis. First, the lesion model for human umbilical vein endothelial cells (HUVECs) was favorably constructed. Later, through RNA-sequencing and bioinformatics analyses, miR-342-5p was identified in lesion model for HUVECs. MiR-342-5p overexpression or knockdown evidently promoted or inhibited the apoptosis of HUVECs impaired by H O . Mechanistically, PPP1R12B was found to have great potential as a target of miR-342-5p in HUVECs impaired by H O , supported by RNA-sequencing and a series of bioinformatics analyses. Meanwhile, the effect of miR-342-5p on PPP1R12B expression in HUVECs’ lesion model was explored, revealing that miR-342-5p had an inhibitory role in PPP1R12B expression. Additionally, adipose-derived mesenchymal stem cells (ADSCs) in spindle-like shape and their derived exosomes with 30 to 150 nm diameter were characterized. Furthermore, results showed miR-342-5p was evidently decreased in the presence of ADSCs-derived exosomes. These findings indicated ADSCs-derived exosomes restrained the expression of miR-324-5p in lesion model. Collectively, this work demonstrates an atherosclerosis-associated miR-342-5p and reveals a preliminary possible mechanism in which miR-342-5p mediated by ADSCs-derived exosomes protects endothelial cells against atherosclerosis.
机译:据报道,外来体介导了几种与疾病相关的微小RNA(miRNA),以影响包括动脉粥样硬化在内的疾病的发展。在这里,我们旨在筛选与动脉粥样硬化相关的miRNA,并初步研究动脉粥样硬化的潜在调控机制。首先,有利地构建了人脐静脉内皮细胞(HUVEC)的病变模型。后来,通过RNA测序和生物信息学分析,在HUVEC的病变模型中发现了miR-342-5p。 MiR-342-5p的过表达或敲低明显促进或抑制了H O损伤的HUVEC的凋亡。从机理上讲,在RNA测序和一系列生物信息学分析的支持下,发现PPP1R12B具有作为miR-342-5p靶标的潜力,该靶点受H O损伤的HUVEC中。同时,研究了miR-342-5p对HUVEC病灶模型中PPP1R12B表达的影响,揭示了miR-342-5p对PPP1R12B表达具有抑制作用。此外,表征了纺锤状形状的脂肪来源的间充质干细胞(ADSC)及其衍生的直径为30至150 nm的外来体。此外,结果显示,在ADSCs衍生的外泌体存在下,miR-342-5p明显降低。这些发现表明,ADSCs衍生的外来体抑制了病变模型中miR-324-5p的表达。总的来说,这项工作证明了与动脉粥样硬化相关的miR-342-5p,并揭示了由ADSCs衍生的外来体介导的miR-342-5p保护内皮细胞免受动脉粥样硬化的可能的初步机制。

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