Circulating miR-375 as a Biomarker of β-Cell Death and Diabetes in Mice
Circulating miR-375 as a Biomarker of β-Cell Death and Diabetes in Mice
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DOI：
10.1210/en.2012-1744
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发表时间：
2013-02-01
期刊：
影响因子：
4.8
通讯作者：
Kieffer, Timothy J.
中科院分区：
文献类型：
--
作者：
Erener, Suheda;Mojibian, Majid;Kieffer, Timothy J.
1型糖尿病是一种进行性自身免疫性疾病，在其初始阶段基本上是沉默的。然而，缺乏用于检测β细胞死亡以及预测和预防糖尿病的敏感方法。在体液中发现了高浓度的微小RNA（miRNAs）。在这项研究中，我们应该确定胰岛富集的miRNA，miR-375是否是检测小鼠β细胞死亡和预测糖尿病的合适血液标志物。我们通过定量RT-PCR检测了链脲佐菌素（STZ）治疗的C57 BL/6小鼠和非肥胖糖尿病（NOD）小鼠血浆样本中miR-375的水平。我们还测量了在细胞死亡抑制剂存在或不存在的情况下细胞因子或STZ处理的胰岛的培养基样品中的miR-375水平。在高血糖症发作之前，高剂量STZ给药显著增加了循环miR-375水平。类似地，在自身免疫性糖尿病的NOD小鼠模型中，循环miR-375水平在糖尿病发作前2周显著增加。此外，在分离的小鼠胰岛中，精氨酸和STZ诱导的细胞死亡使细胞外miR-375水平显著增加，细胞死亡抑制剂可降低细胞外miR-375水平。这些数据表明，循环miR-375可用作β细胞死亡的标志物和糖尿病的潜在预测因子。（内分泌学154：603-608，2013）
Type 1 diabetes is a progressive autoimmune disease that is largely silent in its initial stages. Yet, sensitive methods for detection of beta-cell death and prediction and prevention of diabetes are lacking. Micro-RNAs (miRNAs) have been found at high concentrations in body fluids. Here in this studywesought to determine whetheranislet enrichedmiRNA, miR-375, is a suitable blood marker to detect beta-cell death and predict diabetes in mice. We measured miR-375 levels by quantitative RT-PCR in plasma samples of streptozotocin (STZ)-treated C57BL/6 mice and nonobese diabetic (NOD) mice. We also measured miR-375 levels in media samples of cytokine- or STZ-treated islets in the presence or absence of cell-death inhibitors. High-dose STZ administration dramatically increased circulating miR-375 levels, prior to the onset of hyperglycemia. Similarly, in the NOD mouse model of autoimmune diabetes, circulating miR-375 levels were significantly increased 2 weeks before diabetes onset. Moreover, cytokine-and STZ-induced cell death in isolated mouse islets produced a striking increase in extracellular miR-375 levels, which was reduced by cell death inhibitors. These data suggest that circulating miR-375 can be used as a marker of beta-cell death and potential predictor of diabetes. (Endocrinology 154: 603-608, 2013)