Myostatin blockade improves function but not histopathology in a murine model of limb-girdle muscular dystrophy 2C
Myostatin blockade improves function but not histopathology in a murine model of limb-girdle muscular dystrophy 2C
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DOI：
10.1002/mus.20920
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发表时间：
2008-03-01
期刊：
影响因子：
3.4
通讯作者：
Khurana, Tejvir S.
中科院分区：
文献类型：
--
作者：
Bogdanovich, Sasha;Mcnally, Elizabeth M.;Khurana, Tejvir S.
肌生长抑制素是骨骼肌生长的负调节因子。肌生长抑制素突变和药物策略会增加体内肌肉质量，这表明肌生长抑制素阻断剂可能对以肌肉萎缩为特征的疾病（如肌肉萎缩症）有用。我们将gamma- sarcoglycani -deficient （Sgcg(-/-)）四肢带状肌营养不良（LGMD） 2C小鼠模型进行体内抗体介导的肌生长抑制素阻断。抑制肌肉生长抑制素导致纤维大小、肌肉质量和绝对力量的增加。然而，肌肉组织病理学没有明显的改善，表明生理和组织学改善之间的不一致。这些结果和先前对先天性肌营养不良的dy(w)/dy(w)小鼠模型和LGMD2F的晚期三角肌糖蛋白缺陷（Sgcd(-/-)）小鼠模型的研究表明，在更严重的不同肌营养不良的小鼠模型中，基于肌生长抑制素阻断的治疗策略存在疾病特异性局限性。
Myostatin is a negative regulator of skeletal muscle growth. Myostatin mutations and pharmacological strategies increase muscle mass in vivo, suggesting that myostatin blockade may prove useful in diseases characterized by muscle wasting, such as the muscular dystrophies. We subjected the gamma-sarcoglycan-deficient (Sgcg(-/-)) mouse model of limb-girdle muscular dystrophy (LGMD) 2C to antibody-mediated myostatin blockade in vivo. Myostatin inhibition led to increased fiber size, muscle mass, and absolute force. However, no clear improvement in muscle histopathology was evident, demonstrating discordance between physiological and histological improvement. These results and previous studies on the dy(w)/dy(w) mouse model of congenital muscular dystrophy and in the late-stage delta-sarcoglycan-deficient (Sgcd(-/-)) mouse model of LGMD2F document disease-specific limitations to therapeutic strategies based on myostatin blockade in the more severe mouse models of different muscular dystrophies.