MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle
MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle
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DOI：
10.1007/s00424-014-1517-z
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发表时间：
2015-02
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影响因子：
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通讯作者：
Shogo Wada;Y. Kato;Shuji Sawada;K. Aizawa;Jonghoon Park;A. Russell;T. Ushida;T. Akimoto
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文献类型：
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作者：
Shogo Wada;Y. Kato;Shuji Sawada;K. Aizawa;Jonghoon Park;A. Russell;T. Ushida;T. Akimoto
骨骼肌包含几种不同类型的肌纤维，它们的收缩和代谢特性不同。在过去的几十年里，对纤维类型规范和适应的转录控制进行了深入的研究。近年来，microRNA(MiRNA)介导的转录后基因调控受到越来越多的关注。MIR-23a靶向调节骨骼肌收缩和代谢特性的关键分子，如肌球蛋白重链和过氧化物酶体增殖物激活受体γ，共激活物1α(pGC-1α)。在本研究中，我们分析了miR-23a转基因(miR-23a TG)小鼠的骨骼肌表型，以探讨强制表达miR-23a是否影响4周自愿车轮跑步诱导的线粒体含量、肌肉纤维组成和肌肉适应的标志物。与野生型小鼠相比，mIR-23aTG小鼠的慢比目鱼肌线粒体膜蛋白含量的α和细胞色素氧化酶复合体IV(COX IV)显著降低，而快速足底肌细胞色素氧化酶复合体IV(COX IV)的含量无明显变化。仅TG组小鼠比目鱼肌内Iid/x型纤维减少。经过4周的自愿车轮运动后，耐力运动能力和几种肌肉适应性反应没有差异，包括肌肉质量、毛细血管密度或肌球蛋白重链IIa、PGC-1α、环氧合酶IV和细胞色素的蛋白质含量增加。这些结果表明，miR-23a靶向PGC-1α，并调节慢而不是快的抽动肌肉的基本代谢特性。MiR-23a水平的升高不会影响全身的耐力能力或快速足底肌肉中运动诱导的肌肉适应。
Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. MiR-23a targets key molecules regulating contractile and metabolic properties of skeletal muscle, such as myosin heavy-chains and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α). In the present study, we analyzed the skeletal muscle phenotype of miR-23a transgenic (miR-23a Tg) mice to explore whether forced expression of miR-23a affects markers of mitochondrial content, muscle fiber composition, and muscle adaptations induced by 4 weeks of voluntary wheel running. When compared with wild-type mice, protein markers of mitochondrial content, including PGC-1α, and cytochromecoxidase complex IV (COX IV), were significantly decreased in the slow soleus muscle, but not the fast plantaris muscle of miR-23a Tg mice. There was a decrease in type IId/x fibers only in the soleus muscle of the Tg mice. Following 4 weeks of voluntary wheel running, there was no difference in the endurance exercise capacity as well as in several muscle adaptive responses including an increase in muscle mass, capillary density, or the protein content of myosin heavy-chain IIa, PGC-1α, COX IV, and cytochromec. These results show that miR-23a targets PGC-1α and regulates basal metabolic properties of slow but not fast twitch muscles. Elevated levels of miR-23a did not impact on whole body endurance capacity or exercise-induced muscle adaptations in the fast plantaris muscle.