Sci Transl Med：修复肌营养不良症中细胞损伤的蛋白

据一项刊登在国际著名杂志Science Translational Medicine上的研究报道，提高一种自然产生的能修复损伤细胞的蛋白质的水平可能令罹患杜氏肌营养不良症（DMD）的患者受益。DMD是一种主要影响男性的进行性肌肉消耗性疾病。

DMD是由肌纤维中的肌营养不良蛋白基因的突变引起的，DMD是肌营养不良症的最常见的流行形式。患者通常无法活过青少年时期，且此病无法治愈。

Noah Weisleder及其同事展示，给患有DMD样疾病的小鼠注射大量的重组MG53蛋白可减轻肌肉的损伤。就像是一名机修工给漏气的轮胎打补丁一样，该蛋白会与受损肌肉细胞的细胞膜结合并将其封闭。

一则相关的《焦点》文章写道，MG53成为不断增加的新近研发出来的疗法名录中的一员，这些疗法在小鼠DMD模型中显示出了治疗该疾病的希望。

doi:10.1126/scitranslmed.3003921
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Recombinant MG53 Protein Modulates Therapeutic Cell Membrane Repair in Treatment of Muscular Dystrophy

Noah Weisleder1,2,*, Norio Takizawa2, Peihui Lin1, Xianhua Wang3, Chunmei Cao3, Yan Zhang3, Tao Tan2, Christopher Ferrante2, Hua Zhu1, Pin-Jung Chen2, Rosalie Yan2, Matthew Sterling1, Xiaoli Zhao1, Moonsun Hwang1, Miyuki Takeshima4, Chuanxi Cai1, Heping Cheng3, Hiroshi Takeshima4, Rui-Ping Xiao3 and Jianjie Ma1,2,*

Mitsugumin 53 (MG53), a muscle-specific TRIM family protein, is an essential component of the cell membrane repair machinery. Here, we examined the translational value of targeting MG53 function in tissue repair and regenerative medicine. Although native MG53 protein is principally restricted to skeletal and cardiac muscle tissues, beneficial effects that protect against cellular injuries are present in nonmuscle cells with overexpression of MG53. In addition to the intracellular action of MG53, injury to the cell membrane exposes a signal that can be detected by MG53, allowing recombinant MG53 protein to repair membrane damage when provided in the extracellular space. Recombinant human MG53 (rhMG53) protein purified from Escherichia coli fermentation provided dose-dependent protection against chemical, mechanical, or ultraviolet-induced damage to both muscle and nonmuscle cells. Injection of rhMG53 through multiple routes decreased muscle pathology in the mdx dystrophic mouse model. Our data support the concept of targeted cell membrane repair in regenerative medicine, and present MG53 protein as an attractive biological reagent for restoration of membrane repair defects in human diseases.