Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.
Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.
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血浆来源的外泌体特征揭示了长持续时间1型糖尿病中明显的microRNA特征。
DOI：
10.1038/s41598-017-05787-y
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发表时间：
2017-07-20
影响因子：
4.6
通讯作者：
Ricordi C
中科院分区：
文献类型：
--
作者：
Garcia-Contreras M;Shah SH;Tamayo A;Robbins PD;Golberg RB;Mendez AJ;Ricordi C
1型糖尿病（T1 DM）是由自身免疫攻击产生胰岛素的胰岛β细胞导致慢性高血糖症。外泌体是来源于细胞多泡体的脂质囊泡，其富含特异性miRNA，可能提供疾病特异性诊断特征。为了评估外泌体miRNA作为T1 DM生物标志物的价值，测量了血浆来源的外泌体中的miRNA表达。纳米颗粒跟踪分析和透射电子显微镜证实了通过差速离心分离的血浆来源的外泌体（EXO）的存在。从12名T1 DM和12名对照受试者的血浆来源的EXO提取的总RNA与Nanostring人v2 miRNA微阵列杂交，并在nSolver分析软件上分析表达数据。我们发现7种不同的miRNAs（1种上调，6种下调）在T1 DM中差异表达。通过对24名T1 DM受试者和24名对照受试者的队列进行qRT-PCR分析来验证所选择的候选miRNA。大多数失调的miRNA参与T1 DM的进展。这些发现强调了EXOs miRNA谱在诊断中的潜力，以及对T1 DM分子机制的新见解。
Type 1 diabetes mellitus (T1DM) results from an autoimmune attack against the insulin-producing ß cells which leads to chronic hyperglycemia. Exosomes are lipid vesicles derived from cellular multivesicular bodies that are enriched in specific miRNAs, potentially providing a disease-specific diagnostic signature. To assess the value of exosome miRNAs as biomarkers for T1DM, miRNA expression in plasma-derived exosomes was measured. Nanoparticle tracking analysis and transmission electron microscopy confirmed the presence of plasma-derived exosomes (EXOs) isolated by differential centrifugation. Total RNA extracted from plasma-derived EXOs of 12 T1DM and 12 control subjects was hybridized onto Nanostring human v2 miRNA microarray array and expression data were analyzed on nSolver analysis software. We found 7 different miRNAs (1 up-regulated and 6 down-regulated), that were differentially expressed in T1DM. The selected candidate miRNAs were validated by qRT-PCR analysis of cohorts of 24 T1DM and 24 control subjects. Most of the deregulated miRNAs are involved in progression of T1DM. These findings highlight the potential of EXOs miRNA profiling in the diagnosis as well as new insights into the molecular mechanisms involved in T1DM.
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