Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training
Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training
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DOI：
10.1113/jphysiol.2013.255695
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发表时间：
2013-09-15
影响因子：
5.5
通讯作者：
Akimoto, Takayuki
中科院分区：
文献类型：
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作者：
Russell, Aaron P.;Lamon, Severine;Akimoto, Takayuki
center dot微RNA（miRNAs）的发现建立了控制健康的新机制，但对骨骼肌miRNAs的调节作用知之甚少exercise.center这项研究调查了miRNAs生物合成途径的组成部分。（Drosha，Dicer和Exportin-5），肌肉富集的miRNA，（miR-1，-133 a，-133 b和206）和几种miRNA在肌肉肌病中失调，并显示在急性运动回合后3小时，Drosha，Dicer和Exportin-5，以及miR-1，-133 a，miR-133-B和miR-181 a均增加，而miR-9、-23 a、-23 B和-31减少decreased.center短期训练增加了miR-1和miR-29 B，而miR-31保持减少。中心点在miR-31与HDAC 4蛋白、miR-31与HDAC 4蛋白以及miR-31与NRF 1蛋白之间观察到负相关性exercise.centeractivity.center。运动后骨骼肌细胞中的微小RNA（microRNA，miRNAs）是一种快速、瞬时调控多种微小RNA的分子，可能参与骨骼肌再生、基因转录和线粒体生物合成的调控。本研究调查了miRNA生物发生途径的组分（Drosha、Dicer和Exportin-5）、肌肉富集的miRNA（miR-1、-133a、-133b和-206）以及肌肉肌病中失调的几种miRNA（miR-9、-23、-29、-31和-181）的mRNA调控。测量肌肉活检从9个健康的未经训练的男性在休息，3小时后，急性回合的中等强度的耐力自行车和10天的耐力训练。生物信息学分析用于预测潜在的miRNA靶点。在急性运动后3 h内，Drosha、Dicer和Exportin-5以及miR-1、-133 a、-133-B和-181 a均升高。相反，miR-9、-23a、-23b和-31减少。短期训练增加了miR-1和-29b，而miR-31仍然减少。运动后3 h，miR-9与HDAC 4蛋白（r=-0.71; P= 0.04）、miR-31与HDAC 4蛋白（r =-0.87; P= 0.026）、miR-31与NRF 1蛋白（r =-0.77; P= 0.01）呈负相关。miR-31与HDAC 4和NRF 13非翻译区（UTR）的结合降低了荧光素酶报告基因活性。运动快速和短暂地调节肌肉中的几种miRNA。这些miRNAs中的一些可能参与骨骼肌再生、基因转录和线粒体生物合成的调节。确定耐力运动介导的调节骨骼肌miRNAs的应激信号，以及验证它们的目标和运动后的调节途径，将促进我们对它们在人类健康中的潜在作用的理解。
center dot The discovery of microRNAs (miRNAs) has established new mechanisms that control health, but little is known about the regulation of skeletal muscle miRNAs in response to exercise.center dot This study investigated components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and 206), and several miRNAs dysregulated in muscle myopathies, and showed that 3 h following an acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and miR-181a were all increased, while miR-9, -23a, -23b and -31 were decreased.center dot Short-term training increased miR-1 and miR-29b, while miR-31 remained decreased.center dot Negative correlations were observed between miR-9 and HDAC4 protein, miR-31 and HDAC4 protein and between miR-31 and NRF1 protein, 3 h after exercise.center dot miR-31 binding to the HDAC4 and NRF1 3 untranslated region (UTR) reduced luciferase reporter activity.center dot Exercise rapidly and transiently regulates several miRNA species potentially involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis.Abstract The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3 untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.