Mendler L, Zádor E, Ver Heyen M, Dux L, Wuytack F
Institute of Biochemistry, Faculty of Medicine, University of Szeged, Hungary.
J Muscle Res Cell Motil. 2000;21(6):551-63. doi: 10.1023/a:1026542303629.
Myostatin is a newly described member of the TGF-beta superfamily acting as a secreted negative regulator of skeletal muscle mass in several species, but whose mode of action remains largely unknown. In the present work, we followed the myostatin mRNA and protein levels in rat soleus and extensor digitorum longus (EDL) muscles regenerating in vivo from notexin-induced necrosis, and the myostatin transcript levels in two different in vitro myogenic differentiation models: i.e. in mouse BC3H1 and C2Cl2 cultured cells. The in vivo regenerating rat skeletal muscles showed a characteristic time-dependent expression of myostatin mRNA. After notexin injection, the transcript levels dropped below the detection limit on day 1 in soleus and close to the detection limit on day 3 in EDL, then increased to a maximum on day 7 in soleus and after 28 days finally reached the control values in both types of muscles. In contrast, the myostatin protein levels increased dramatically on the first days of regeneration in both muscles, i.e. at the time when its transcript level was low. Later on the myostatin protein level gradually declined to normal in soleus while in EDL it stayed high some days longer and decreased to normal on days 21-28. In vitro proliferating myoblasts produced low level of myostatin mRNA, which increased upon induction of differentiation suggesting that functional innervation is no prerequisite for myostatin expression. Myostatin production in vitro seems not to be dependent on myocyte fusion either, since it is observed in differentiated BC3H1 cells, which are defective in myofiber formation.
肌肉生长抑制素是转化生长因子-β超家族新发现的成员，在多个物种中作为骨骼肌质量的分泌型负调控因子，但目前其作用模式仍不清楚。在本研究中，我们追踪了大鼠比目鱼肌和趾长伸肌（EDL）在体内因蛇毒蛋白诱导坏死而再生时的肌肉生长抑制素mRNA和蛋白水平，以及在两种不同的体外成肌分化模型中的肌肉生长抑制素转录水平：即小鼠BC3H1和C2Cl2培养细胞。体内再生的大鼠骨骼肌呈现出肌肉生长抑制素mRNA特征性的时间依赖性表达。注射蛇毒蛋白后，比目鱼肌中第1天转录水平降至检测限以下，EDL中第3天接近检测限，然后比目鱼肌在第7天升至最高，最终两种肌肉在28天后均达到对照值。相反，两种肌肉在再生的最初几天肌肉生长抑制素蛋白水平均显著升高，即其转录水平较低时。随后，比目鱼肌中肌肉生长抑制素蛋白水平逐渐降至正常，而在EDL中则在较长时间内保持较高水平，并在第21 - 28天降至正常。体外增殖的成肌细胞产生低水平的肌肉生长抑制素mRNA，诱导分化后其水平升高，这表明功能性神经支配并非肌肉生长抑制素表达的必要条件。体外肌肉生长抑制素的产生似乎也不依赖于肌细胞融合，因为在分化的BC3H1细胞中也观察到了这种情况，而这些细胞在肌纤维形成方面存在缺陷。
