Department of Neurosurgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250000, Shandong Province, P.R. China.
Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng 250000, Shandong Province, P.R. China.
Aging (Albany NY). 2020 Feb 24;12(4):3880-3898. doi: 10.18632/aging.102857.
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 HO. Mechanistically, PPP1R12B was found to have great potential as a target of miR-342-5p in HUVECs impaired by HO, 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.
外泌体被报道能介导几种与疾病相关的 microRNAs(miRNAs),影响疾病的进展,包括动脉粥样硬化。在这里,我们旨在筛选与动脉粥样硬化相关的 miRNAs,并初步探讨动脉粥样硬化的潜在调控机制。首先,构建了人脐静脉内皮细胞(HUVECs)病变模型。随后,通过 RNA 测序和生物信息学分析,在 HUVECs 病变模型中鉴定出 miR-342-5p。miR-342-5p 的过表达或敲低明显促进或抑制了 HO 损伤的 HUVECs 的凋亡。从机制上讲,通过 RNA 测序和一系列生物信息学分析,发现 PPP1R12B 作为 HO 损伤的 HUVECs 中 miR-342-5p 的靶基因具有很大的潜力。同时,探讨了 miR-342-5p 对 HUVECs 病变模型中 PPP1R12B 表达的影响,揭示了 miR-342-5p 对 PPP1R12B 表达具有抑制作用。此外,对呈纺锤形的脂肪间充质干细胞(ADSCs)及其直径为 30 至 150nm 的衍生外泌体进行了鉴定。此外,结果表明 ADSCs 衍生的外泌体中 miR-342-5p 的表达明显降低。这些发现表明 ADSCs 衍生的外泌体抑制了病变模型中 miR-324-5p 的表达。总之,这项工作证明了一种与动脉粥样硬化相关的 miR-342-5p,并揭示了 ADSCs 衍生的外泌体介导 miR-342-5p 的初步可能机制,该机制保护内皮细胞免受动脉粥样硬化的影响。