Opposite roles of myocardin and atrogin-1 in L6 myoblast differentiation.
Opposite roles of myocardin and atrogin-1 in L6 myoblast differentiation.
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心肌素和 atrogin-1 在 L6 成肌细胞分化中的相反作用。
DOI：
10.1002/jcp.24365
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发表时间：
2013
影响因子：
5.6
通讯作者：
LibinCardiovascularInstituteofAlberta
中科院分区：
文献类型：
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作者：
Jiang,Yulan;Singh,Pavneet;Yin,Hao;Zhou,Yi-Xia;Gui,Yu;Wang,Da-Zhi;Zheng,Xi-Long;SmoothMuscleResearchGroup;LibinCardiovascularInstituteofAlberta
当在含有低浓度血清的培养基中培养时，L 6大鼠成肌细胞经历分化和肌管形成，但其潜在机制尚不清楚。atrogin-1是一种在肌肉萎缩中具有良好特征的E3连接酶，其在肌肉分化中的作用尚未确定。肌钙蛋白是血清反应因子（SRF）的共激活物，其共同促进平滑肌分化。肌钙蛋白在骨骼肌祖细胞中瞬时表达，对肌细胞生成素的表达和肌肉分化具有抑制作用。它仍然是未知的，是否心肌蛋白，经历泛素化降解，在L 6细胞分化中发挥作用。本研究旨在研究myocardin和atrogin-1在L 6细胞分化中的潜在作用。正如许多其他人所报道的，转移到含有2%血清的培养基诱导L 6细胞的肌管形成。分化伴随着atrogin-1的上调和myocardin的下调，这表明两者都可能参与肌肉分化。正如预期的那样，atrogin-1的过度表达刺激了肌钙蛋白T和肌细胞生成素的表达以及L 6成肌细胞的分化。心肌蛋白与atrogin-1的共表达抑制atrogin-1诱导的肌细胞生成素表达。atrogin-1的过表达降低了心肌蛋白的蛋白水平，但不影响其mRNA水平。小干扰RNA介导的atrogin-1敲低增加了心肌蛋白。因此，myocardin的异位表达抑制肌细胞分化。出乎意料的是，myocardin降低了atrogin-1的表达，而不涉及Foxo 1。总之，我们的结果表明，atrogin-1通过下调myocardin在骨骼肌分化中起着积极的作用。J.细胞。228：1989-1995，2013。© 2013 Wiley Periodicals，Inc.
L6 rat myoblasts undergo differentiation and myotube formation when cultured in medium containing a low‐concentration of serum, but the underlying mechanism is not well understood. The role of atrogin‐1, an E3 ligase with well‐characterized roles in muscle atrophy, has not been defined in muscle differentiation. Myocardin is a coactivator of serum response factor (SRF), which together promotes smooth muscle differentiation. Myocardin is transiently expressed in skeletal muscle progenitor cells with inhibitory effects on the expression of myogenin and muscle differentiation. It remains unknown whether myocardin, which undergoes ubiquitination degradation, plays a role in L6 cell differentiation. The current study aimed to investigate the potential roles of myocardin and atrogin‐1 in differentiation of L6 cells. As reported by many others, shifting to medium containing 2% serum induced myotube formation of L6 cells. Differentiation was accompanied by up‐regulation of atrogin‐1 and down‐regulation of myocardin, suggesting that both may be involved in muscle differentiation. As expected, over‐expression of atrogin‐1 stimulated the expression of troponin T and myogenin and differentiation of the L6 myoblasts. Co‐expression of myocardin with atrogin‐1 inhibited atrogin‐1‐induced myogenin expression. Over‐expression of atrogin‐1 decreased myocardin protein level, albeit without affecting its mRNA level. Small‐interfering RNA‐mediated knockdown of atrogin‐1 increased myocardin protein. Consistently, ectopic expression of myocardin inhibited myogenic differentiation. Unexpectedly, myocardin decreased the expression of atrogin‐1 without involving Foxo1. Taken together, our results have demonstrated that atrogin‐1 plays a positive role in skeletal muscle differentiation through down‐regulation of myocardin. J. Cell. Physiol. 228: 1989–1995, 2013. © 2013 Wiley Periodicals, Inc.