Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells.
Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells.
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DOI：
10.1371/journal.pone.0062008
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Eckel J
中科院分区：
文献类型：
--
作者：
Raschke S;Eckardt K;Bjørklund Holven K;Jensen J;Eckel J
骨骼肌分泌的蛋白质，即所谓的肌因子，已被证明可以影响肌肉生理，并对其他组织和器官产生全身性影响。尽管最近的分析研究已经确定了许多肌肉因子，但这些研究的重叠量表明骨骼肌分泌组的特征仍然不完全。所使用的模型的一个限制是缺乏收缩，这是肌肉细胞的一个主要特征。在这里，我们旨在通过细胞因子抗体阵列来表征原代人肌管的分泌组，并鉴定受电脉冲刺激（EPS）诱导的收缩调节的肌因子。在这项研究中，我们验证了两种选定的肌肉因子的调节和释放，即色素上皮衍生因子（PEDF）和二肽基肽酶4 (DPP4)，它们最近被称为脂肪因子。本研究表明，DPP4和PEDF这两种因子都是由原代人肌管分泌的。PEDF是一种收缩调节的肌因子，尽管健康年轻男性的PEDF血清水平在VO2max为70%时骑行60分钟后会下降。最有趣的是，我们发现了52种新的肌肉因子，这些因子以前没有被描述过，是由骨骼肌细胞分泌的。对于48种肌因子，我们发现它们的释放受收缩活动的调节。这项对人类骨骼肌分泌组的分析研究扩大了肌因子的数量，确定了新的收缩调节的肌因子，并强调了脂肪因子和肌因子蛋白质之间的重叠。
Proteins secreted by skeletal muscle, so called myokines, have been shown to affect muscle physiology and additionally exert systemic effects on other tissues and organs. Although recent profiling studies have identified numerous myokines, the amount of overlap from these studies indicates that the secretome of skeletal muscle is still incompletely characterized. One limitation of the models used is the lack of contraction, a central characteristic of muscle cells. Here we aimed to characterize the secretome of primary human myotubes by cytokine antibody arrays and to identify myokines regulated by contraction, which was induced by electrical pulse stimulation (EPS). In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. PEDF is a contraction-regulated myokine, although PEDF serum levels from healthy young men decrease after 60 min cycling at VO2max of 70%. Most interestingly, we identified 52 novel myokines which have not been described before to be secreted by skeletal muscle cells. For 48 myokines we show that their release is regulated by contractile activity. This profiling study of the human skeletal muscle secretome expands the number of myokines, identifies novel contraction-regulated myokines and underlines the overlap between proteins which are adipokines as well as myokines.
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