Injury factors alter miRNAs profiles of exosomes derived from islets and circulation
Injury factors alter miRNAs profiles of exosomes derived from islets and circulation
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损伤因素改变来自胰岛和循环系统的外泌体的 miRNA 谱
DOI：
10.18632/aging.101689
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发表时间：
2018-12-01
期刊：
影响因子：
5.2
通讯作者：
Yang, Tao
中科院分区：
文献类型：
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作者：
Fu, Qi;Jiang, Hemin;Yang, Tao
胰岛损伤是糖尿病的一种主要异常表现。最近的研究提示外切体在诊断中的价值。本研究旨在探讨损伤因素对胰岛外体miRNA谱的影响，并确定循环外体miRNAs是否适合作为胰岛损伤的生物标志物。分离小鼠胰岛，用混合细胞因子(肿瘤坏死因子-α、白介素1-β和干扰素-γ)或链脲佐菌素(STZ)诱导体外损伤，并从培养上清液中提取外切体。利用miRNA芯片分析，我们发现在STZ和细胞因子处理的胰岛外体中分别有22和11个差异表达的miRNAs，其中6个miRNAs作为两种损伤条件的交集。其中MMU-miR-375-3p和MMU-miR-129-5p可通过qRT-PCR进行验证。然后，从注射STZ的小鼠和不同糖代谢状态和糖尿病病程的受试者中分离血清外切体。QRT-PCR显示，在血糖和胰岛素紊乱之前，STZ处理的小鼠血清中外体MMU-miR-375-3p显著升高。在新发糖尿病患者中，hsa-miR-375-3p在人血清外体中升高。总之，我们的结果表明，损伤因素改变了胰岛来源的外体的miRNA图谱，外体miR-375-3p有望成为胰岛损伤的生物标志物。
Islets damage is a major abnormality underling diabetes. Recent studies suggested the value of exosomes in diagnosis. This study aimed to investigate the impact of injury factors on the miRNA profiles of islet exosomes and determine whether circulating exosomal miRNAs is suitable as biomarkers of islets damage. Islets were isolated from ICR mice and induced injury in vitro by mixed cytokines (Tumor Necrosis Factor-α, Interleukin -1β and Interferon-γ) or streptozotocin (STZ), and exosomes were derived from the cultural supernatant. Using miRNA microarray analysis, we found 22 and 11 differentially expressed miRNAs in islet exosomes of STZ and cytokines treatment, respectively, including 6 miRNAs as the intersection of two injured conditions. Thereinto, mmu-miR-375-3p and mmu-miR-129-5p could be validated by qRT-PCR. Then, Serum exosomes were isolated from STZ injected mice and subjects with various glucose metabolism states and diabetic duration. qRT-PCR demonstrated exosomal mmu-miR-375-3p dramatically increased in serum of STZ treated mouse prior to the disturbance of blood glucose and insulin. In human serum exosomes, hsa-miR-375-3p was elevated in new-onset diabetes patients. Overall, our results suggest that injury factors changed miRNA profiles of exosomes derived from islets and exosomal miR-375-3p showed promising potential as a biomarker of islets damage.