Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy.
Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy.
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DOI：
10.1126/scitranslmed.3003921
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发表时间：
2012-06-20
影响因子：
17.1
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Weisleder N;Takizawa N;Lin P;Wang X;Cao C;Zhang Y;Tan T;Ferrante C;Zhu H;Chen PJ;Yan R;Sterling M;Zhao X;Hwang M;Takeshima M;Cai C;Cheng H;Takeshima H;Xiao RP;Ma J
mitsugumin53 （MG53）是一种肌肉特异性TRIM家族蛋白，是细胞膜修复机制的重要组成部分。在这里，我们研究了靶向MG53功能在组织修复和再生医学中的翻译价值。虽然天然MG53蛋白仅限于骨骼肌和心肌组织，但在MG53过表达的非肌肉细胞中也存在保护细胞免受损伤的有益作用。除了MG53在细胞内的作用外，对细胞膜的损伤暴露出MG53可以检测到的信号，使得重组MG53蛋白在细胞外空间提供时能够修复膜损伤。从大肠杆菌发酵中纯化的重组人MG53 （rhMG53）蛋白对肌肉和非肌肉细胞的化学、机械或紫外线诱导的损伤均具有剂量依赖的保护作用。通过多种途径注射rhMG53可降低mdx营养不良小鼠模型的肌肉病理。我们的数据支持再生医学中靶向细胞膜修复的概念，并表明MG53蛋白是修复人类疾病中膜修复缺陷的一种有吸引力的生物试剂。
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 restricted to skeletal and cardiac muscle tissues, beneficial effects that protect against cellular injuries are present in non-muscle 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 UV-induced damage to both muscle and non-muscle 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.
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影响因子：
6
作者：
Chase, Thomas H.;Cox, Gregory A.;Shultz, Leonard D.
通讯作者：
Shultz, Leonard D.
影响因子：
56.9
作者：
FONG, P;TURNER, PR;STEINHARDT, RA
通讯作者：
STEINHARDT, RA
影响因子：
7.8
作者：
Fujiwara, Takahiro;Ritchie, Ken;Murakoshi, Hideji;Jacobson, Ken;Kusumi, Akihiro
通讯作者：
Kusumi, Akihiro
DOI：
10.1073/pnas.89.10.4524
发表时间：
1992-05-15
影响因子：
11.1
作者：
LEE, RC;RIVER, LP;WOLLMANN, RL
通讯作者：
WOLLMANN, RL
影响因子：
64.8
作者：
Gussoni, E;Soneoka, Y;Mulligan, RC
通讯作者：
Mulligan, RC