Abe Shinichi, Soejima Masakazu, Iwanuma Osamu, Saka Hideki, Matsunaga Satoru, Sakiyama Koji, Ide Yoshinobu
Department of Anatomy, Tokyo Dental College, Chiba-City, Chiba, Japan.
Zoolog Sci. 2009 May;26(5):315-20. doi: 10.2108/zsj.26.315.
Follistatin is a functional antagonist of several members of the TGF-beta family of secreted signaling factors, including myostatin, the most powerful inhibitor of muscle growth characterized to date. Myostatin inhibition offers a novel therapeutic strategy for muscular dystrophy by restoring skeletal muscle mass and suppressing the progression of muscle degeneration. To assess the potential benefits of follistatin in treating muscle degenerative diseases, we examined the expression of myostatin and follistatin in Mdx mice, a model for Duchenne muscular dystrophy, and in B10 mice as a control. Our results demonstrated a temporary and coincident expression of follistatin and myostatin in both mouse strains, but this expression was significantly higher in Mdx mice than in B10 mice. The maximum expression of follistatin and myostatin in the presence of restoring necrotic muscle was detected 4 weeks after birth in Mdx mice. Interestingly, during the stage of complete regeneration, the absence of myostatin and follistatin proteins and a marked decrease in the expression of both genes were observed 9 weeks after birth in both mouse strains. These findings suggest that follistatin not only blocks myostatin but also allows other activators to function in muscle development, emphasizing that follistatin could be a very potent molecule in combating muscle loss during dystrophies and muscle ageing, disuse, or denervation.
卵泡抑素是分泌型信号因子转化生长因子-β（TGF-β）家族多个成员的功能性拮抗剂，其中包括肌肉生长抑制素，它是迄今为止所发现的最强有力的肌肉生长抑制剂。抑制肌肉生长抑制素可通过恢复骨骼肌质量和抑制肌肉退化进程，为治疗肌肉萎缩症提供一种全新的治疗策略。为评估卵泡抑素在治疗肌肉退行性疾病方面的潜在益处，我们检测了杜氏肌营养不良症模型Mdx小鼠以及作为对照的B10小鼠中肌肉生长抑制素和卵泡抑素的表达情况。我们的结果表明，两种小鼠品系中卵泡抑素和肌肉生长抑制素均有短暂且同时出现的表达，但Mdx小鼠中的这种表达显著高于B10小鼠。在Mdx小鼠出生后4周，检测到在坏死肌肉恢复过程中卵泡抑素和肌肉生长抑制素的表达达到最高值。有趣的是，在完全再生阶段，两种小鼠品系在出生后9周均观察到肌肉生长抑制素和卵泡抑素蛋白缺失，且两种基因的表达均显著下降。这些发现表明，卵泡抑素不仅能阻断肌肉生长抑制素，还能使其他激活因子在肌肉发育中发挥作用，这突出了卵泡抑素在对抗营养不良、肌肉衰老、废用或去神经支配过程中肌肉丢失方面可能是一种非常有效的分子。
