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.