Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes.
Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes.
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DOI：
10.1007/s00125-010-1667-2
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发表时间：
2010-06
期刊：
影响因子：
8.2
通讯作者：
Lindgren, C. M.
中科院分区：
文献类型：
--
作者：
Herrera, B. M.;Lockstone, H. E.;Taylor, J. M.;Ria, M.;Barrett, A.;Collins, S.;Kaisaki, P.;Argoud, K.;Fernandez, C.;Travers, M. E.;Grew, J. P.;Randall, J. C.;Gloyn, A. L.;Gauguier, D.;McCarthy, M. I.;Lindgren, C. M.
microRNA调节广泛的生物学机制。为了研究microRNA表达与2型糖尿病之间的关系，我们比较了糖尿病易感性不同的三种近交系大鼠胰岛素靶组织中microRNA的整体表达。使用微阵列，我们测量了283种microRNA在高脂血症（Goto-Kakizaki）、中度脂血症（Wistar京都）和正常脂血症（Brown Norway）大鼠（每种品系n = 5）的脂肪、肝脏和肌肉组织中的表达。比较菌株间的表达，并使用定量RT-PCR进行验证。此外，在暴露于高脂血症条件的3 T3-L1脂肪细胞中研究了脂肪组织中的microRNA表达变化。我们发现了29个显著分化的microRNA（p调整< 0.05）：9个在脂肪组织中，18个在肝脏中，2个在肌肉中。其中，5种microRNA的表达模式与菌株特异性贫血表型相关。miR-222（padjusted = 0.0005）和miR-27 a（padjusted = 0.006）在脂肪组织中上调; miR-195（padjusted = 0.006）和miR-103（padjusted = 0.04）在肝脏中上调; miR-10 b（padjusted = 0.004）在肌肉中下调。将3 T3-L1脂肪细胞暴露于葡萄糖浓度增加的环境中，可上调miR-222（p = 0.008）、miR-27 a（p = 0.02）和之前报道的miR-29 a（p = 0.02）的表达。这些差异表达microRNA的预测靶基因参与2型糖尿病相关通路。miR-222、miR-27 a、miR-195、miR-103和miR-10 b的表达模式随高脂血症而变化，表明这些microRNA在2型糖尿病的病理生理学中的作用，如Gyoto-Kakizaki大鼠所模拟的。我们观察到脂肪细胞中miR-222、miR-27 a和miR-29 a的表达模式相似，作为对葡萄糖水平升高的响应，这支持了我们的假设，即microRNA表达的改变伴随着与2型糖尿病发病机制相关的主要事件。本文的在线版本（doi：10.1007/s 00125 -010-1667-2）包含补充材料，可供授权用户使用。
MicroRNAs regulate a broad range of biological mechanisms. To investigate the relationship between microRNA expression and type 2 diabetes, we compared global microRNA expression in insulin target tissues from three inbred rat strains that differ in diabetes susceptibility. Using microarrays, we measured the expression of 283 microRNAs in adipose, liver and muscle tissue from hyperglycaemic (Goto–Kakizaki), intermediate glycaemic (Wistar Kyoto) and normoglycaemic (Brown Norway) rats (n = 5 for each strain). Expression was compared across strains and validated using quantitative RT-PCR. Furthermore, microRNA expression variation in adipose tissue was investigated in 3T3-L1 adipocytes exposed to hyperglycaemic conditions. We found 29 significantly differentiated microRNAs (padjusted < 0.05): nine in adipose tissue, 18 in liver and two in muscle. Of these, five microRNAs had expression patterns that correlated with the strain-specific glycaemic phenotype. MiR-222 (padjusted = 0.0005) and miR-27a (padjusted = 0.006) were upregulated in adipose tissue; miR-195 (padjusted = 0.006) and miR-103 (padjusted = 0.04) were upregulated in liver; and miR-10b (padjusted = 0.004) was downregulated in muscle. Exposure of 3T3-L1 adipocytes to increased glucose concentration upregulated the expression of miR-222 (p = 0.008), miR-27a (p = 0.02) and the previously reported miR-29a (p = 0.02). Predicted target genes of these differentially expressed microRNAs are involved in pathways relevant to type 2 diabetes. The expression patterns of miR-222, miR-27a, miR-195, miR-103 and miR-10b varied with hyperglycaemia, suggesting a role for these microRNAs in the pathophysiology of type 2 diabetes, as modelled by the Gyoto–Kakizaki rat. We observed similar patterns of expression of miR-222, miR-27a and miR-29a in adipocytes as a response to increased glucose levels, which supports our hypothesis that altered expression of microRNAs accompanies primary events related to the pathogenesis of type 2 diabetes. The online version of this article (doi:10.1007/s00125-010-1667-2) contains supplementary material, which is available to authorised users.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
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12.3
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Zhang J
影响因子：
12.3
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