Circulating miR-143-3p inhibition protects against insulin resistance in Metabolic Syndrome via targeting of the insulin-like growth factor 2 receptor
Circulating miR-143-3p inhibition protects against insulin resistance in Metabolic Syndrome via targeting of the insulin-like growth factor 2 receptor
复制标题
循环 miR-143-3p 抑制通过靶向胰岛素样生长因子 2 受体来防止代谢综合征中的胰岛素抵抗
DOI：
10.1016/j.trsl.2018.09.006
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发表时间：
2019-03-01
影响因子：
7.8
通讯作者：
Li Hong
中科院分区：
文献类型：
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作者：
Lin Xihua;Tang Shengjie;Li Hong
代谢综合征（MetS）的特征在于包括肥胖、血脂异常、高血糖和高血压在内的一系列代谢紊乱。在这里，我们报告了27个microRNA被发现在MetS患者的血清和尿液样本中表达不同，与对照组相比，微阵列分析。进一步的定性真实的时间-聚合酶链反应分析证实，与对照相比，在MetS患者中miR-143- 3 p的循环水平在血清和尿液样品中均显著升高。在考虑混杂因素后，高水平的miR-143- 3 p仍然是胰岛素抵抗的独立危险因素。在小鼠中抑制miR-143- 3 p表达可防止肥胖相关胰岛素抵抗的发展。此外，我们通过检索3个广泛使用的生物信息学数据库并进行初步验证，证明胰岛素样生长因子2受体（IGF 2 R）是miR-143- 3 p的靶基因之一。我们的实验表明，敲低循环miR-143- 3 p可以通过靶向IGF 2 R和激活胰岛素信号通路来保护MetS背景下的胰岛素抵抗。我们的研究结果将miR-143- 3 p-IGF 2 R通路作为治疗肥胖相关胰岛素抵抗的潜在靶点。
Metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including obesity, dyslipidemia, hyperglycemia, and hypertension. Here, we report that 27 microRNAs were found to be expressed differently in serum and urine samples of MetS patients compared to control subjects on microarray analysis. Further qualitative real time- polymerase chain reaction analyses confirmed that circulating levels of miR-143-3p were significantly elevated in MetS patients compared with controls, both in serum and urine samples. After accounting for confounding factors, high levels of miR-143-3p remained an independent risk factor for insulin resistance. Inhibition of miR-143-3p expression in mice protected against development of obesity-associated insulin resistance. Furthermore, we demonstrated that insulin-like growth factor 2 receptor (IGF2R) was among the target genes of miR-143-3p by searching 3 widely used bioinformatics databases and preliminary validation. Our experiments suggest that knockdown of circulating miR-143-3p may protect against insulin resistance in the setting of MetS via targeting of IGF2R and activation of the insulin signaling pathway. Our results characterize the miR-143-3p-IGF2R pathway as a potential target for the treatment of obesity-associated insulin resistance.