RT Journal Article SR Electronic T1 Recombinant MG53 Protein Modulates Therapeutic Cell Membrane Repair in Treatment of Muscular Dystrophy JF Science Translational Medicine FD American Association for the Advancement of Science SP 139ra85 OP 139ra85 DO 10.1126/scitranslmed.3003921 VO 4 IS 139 A1 Weisleder, Noah A1 Takizawa, Norio A1 Lin, Peihui A1 Wang, Xianhua A1 Cao, Chunmei A1 Zhang, Yan A1 Tan, Tao A1 Ferrante, Christopher A1 Zhu, Hua A1 Chen, Pin-Jung A1 Yan, Rosalie A1 Sterling, Matthew A1 Zhao, Xiaoli A1 Hwang, Moonsun A1 Takeshima, Miyuki A1 Cai, Chuanxi A1 Cheng, Heping A1 Takeshima, Hiroshi A1 Xiao, Rui-Ping A1 Ma, Jianjie YR 2012 UL http://stm.sciencemag.org/content/4/139/139ra85.abstract AB 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.