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MSTN：肌肉疾病靶向治疗的关键靶点
368 人阅读发布时间：2025-06-06 14:57
核心信号通路
MSTN主要通过经典TGF-β信号通路抑制肌肉生长，其活性形式与ACVR2型受体结合后，招募激活素受体样激酶（ALK4/5/7），进而磷酸化Smad2/3蛋白，最终抑制成肌细胞增殖与分化 [2,7]。此外，MSTN还能借助非Smad通路，包括ERK1/2、p38MAPK等 [7,12]，对肌肉代谢进行精准调控。例如，在C2C12肌细胞内，MSTN通过抑制AKT信号通路阻断肌管肥大进程，而MSTN敲除操作则会激活AKT，促进肌肉生长 [7]；在牛成肌细胞中，MSTN突变致使Smad2/3磷酸化水平下降，同时上调BMP信号通路，推动成骨分化 [13]。
组织特异性调控
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肌肉发育： 在骨骼肌中呈现高表达状态，对卫星细胞活化和肌纤维肥大发挥抑制作用。研究显示，敲除MSTN的小鼠和绵羊肌纤维数量及直径均显著增长 [6,12]。 -
骨骼与脂肪： 同源蛋白GDF11能激活BMP信号促进成骨，然而MSTN自身却通过抑制成骨细胞分化以及促进破骨细胞生成，引发骨量减少 [7]。在脂肪代谢方面，MSTN抑制脂肪细胞分化，其突变与畜禽脂肪沉积量降低存在关联 [13]。 -
胰腺病理：MSTN基因突变的犊牛会发生胰腺腺泡细胞坏死以及炎症细胞浸润，从而引发致死性胰腺炎，为MSTN参与胰腺稳态调控提供了有力证据 [1]。
肌肉萎缩与肌病
MSTN 过度表达与杜氏肌营养不良（DMD）、衰老相关肌少症等肌肉萎缩疾病密切相关。阻断MSTN信号可改善小鼠模型的肌肉功能 [3,7]。临床试验中，抗MSTN抗体在DMD患者中显示肌肉体积增加，但功能改善有限 [3]。
代谢性疾病
骨骼疾病
MSTN通过抑制成骨细胞活性和促进破骨细胞生成参与骨质疏松。敲除MSTN的绵羊表现出骨密度增加，而抑制GDF11（与MSTN共享受体）则导致骨强度下降 [7]。
● 重组蛋白
Recombinant Human Growth/differentiation factor 8 (MSTN) (Active); CSB-MP015057HU(A4)
● 抗体
MSTN Antibody; CSB-PA11869A0Rb
● ELISA试剂盒
Human Myostatin,MSTN ELISA Kit CSB-E11300h
参考文献：
[1] Yang, M., Wei, Z., Zhou, X., et al. (2020). A Fatal Case of MSTN Mutation Calf Pancreatitis. Preprints.
[2] Maeta, K., Farea, M., Nishio, H., & Matsuo, M. (2023). A novel splice variant of the human MSTN gene encodes a myostatin-specific myostatin inhibitor. Journal of Cachexia, Sarcopenia and Muscle, 14, 2289-2300.
[3] Campbell, C., et al. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle & Nerve, 55(4), 458-464.
[4] Grobet, L., Martin, L. J. R., Poncelet, D., et al. (1997). A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genetics, 17(1), 71-74.
[5] McPherron, A. C., Lawler, A. M., & Lee, S. J. (1997). Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature, 387(6628), 83-90.
[6] Guo, R., Wang, H., Meng, C., et al. (2023). Efficient and Specific Generation of MSTN-Edited Hu Sheep Using C-CRISPR. Genes, 14(6), 1216.
[7] Suh, J., Kim, N. K., Lee, S. H., et al. (2020). GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone. Proceedings of the National Academy of Sciences, 117(9), 4910-4920.
[8] Schuelke, M., Wagner, K. R., Stolz, L. E., et al. (2004). Myostatin mutation associated with gross muscle hypertrophy in a child. New England Journal of Medicine, 350(26), 2682-2688.
[9] Li, R., Zeng, W., Ma, M., et al. (2020). Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs. Transgenic Research, 29(2), 149-163.
[10] Wang, X., Niu, Y., Zhou, J., et al. (2016). Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Scientific Reports, 6, 32271.
[11] McPherron, A. C., & Lee, S. J. (1997). Double muscling in cattle due to mutations in the myostatin gene. Proceedings of the National Academy of Sciences, 94(23), 12457-12461.
[12] Eom, K.-H., Kwon, D.-H., Kim, Y.-C., et al. (2024). Novel Mammalian Ubiquitous Promoter Isolated from Bovine MSTN Gene Promoter. Preprints.
[13] Zhang, C., Liu, Y., Xu, D., et al. (2011). Polymorphisms of myostatin gene (MSTN) in four goat breeds and their effects on Boer goat growth performance. Molecular Biology Reports, 39(3), 3081-3087.
[14] Li, R., Zeng, W., Ma, M., et al. (2020). CRISPR/Cas9-mediated MSTN disruption accelerates the growth of Chinese Bama pigs. Reproduction in Domestic Animals, 55(6), 1314-1327.