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Research Article

miRNA-146a改善类风湿关节炎中MSC衍生外来体的免疫调节作用。

卷 20, 期 4, 2020

页: [297 - 312] 页: 16

弟呕挨: 10.2174/1566523220666200916120708

价格: $65

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摘要

背景：类风湿关节炎（RA）是一种严重的炎症性关节疾病，一些研究已经注意到microRNA（miRNA）在RA发病机理中起重要作用的可能性。 MiR-146和miR-155是主要的免疫反应调节剂。间充质干细胞（MSCs）的免疫调节功能主要受旁分泌因子（如外泌体）的调节。外来体在细胞间通讯中充当遗传信息的载体，可在细胞之间传递miRNA，并已被研究为治疗性分子递送的载体。 目的：目前的研究旨在研究miR-146a / miR-155转导的间充质干细胞（MSC）衍生的外泌体对免疫应答的治疗作用。 方法：在这里，从miR-146a / miR-155过表达的正常MSC中提取外泌体。从胶原诱导的关节炎（CIA）和对照小鼠中分离出脾细胞。然后监测表达水平miR-146a和miR-155。进行流式细胞术以评估外来体对调节性T细胞（Treg）水平的影响。一些关键的自身免疫应答基因及其蛋白产物的表达，包括视黄酸相关的孤儿受体（ROR）-γt，肿瘤坏死因子（TNF）-α，白介素（IL）-17，-6，-10和转化生长使用定量实时PCR和ELISA测定脾细胞中的TGF-β。结果表明，miR-146a主要在CIA小鼠中下调。与对照小鼠相比，用MSC来源的外来体和miR-146a / miR-155转导的MSC来源的外来体进行治疗可显着改变CIA小鼠的Treg细胞水平。 结果：最终，这种调节可促进炎症性疾病（如RA）中适当T细胞反应的恢复。 结论：miR-146a转导的MSC来源的外来体也增加了CIA小鼠的叉头盒P3（Fox-P3），TGFβ和IL-10基因的表达。 miR-155进一步增加了这些小鼠中RORγt，IL-17和IL-6的基因表达。基于此处的发现，外泌体似乎促进了miRNA在细胞之间的直接细胞内转移，并代表了RA的可能治疗策略。用抗炎miRNA操纵MSC衍生的外泌体可能会增加Treg细胞群和抗炎细胞因子。

关键词: 间充质干细胞，microRNA，外来体，类风湿性关节炎，自身免疫性疾病，关节和骨骼。

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