Abstract
MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.
Highlights
MG53 is a muscle-specific tripartite motif (TRIM)-family protein that presides over the cell membrane repair response
As a member of the TRIM-family protein, MG53 contains E3ligase activity which may participate in modulation of metabolic function[20,21]
Error bar represents the standard deviation and p value was generated by t test we found that incubation of mg53−/− muscle fibers with recombinant human MG53 (rhMG53) protein could restore muscle satellite cell (mSC) proliferation
Summary
MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. RhMG53 ameliorates pathology associated with muscular dystrophy, lung injury, myocardial infarction, and acute kidney injury in rodent and large animal models of these diseases[13,17,18,19] These data highlight the importance of targeting cell membrane repair in regenerative medicine and present MG53 as a potential biological reagent for restoration of tissue integrity in a broad range of human diseases. A recent report by Liu et al showed that cardiac-specific overexpression of MG53 induced cardiomyopathy via transcriptional activation of the peroxisome proliferation-activated receptor (PPARα)[30] While these studies raise concerns over the safety of MG53 overexpression on cardiovascular and metabolic function, no studies have been conducted to investigate the physiological impact of elevating MG53 in blood circulation. Physiological and biochemical studies reveal that sustained elevation of MG53 in the bloodstream does not impact the body’s metabolic function of glucose handling and insulin signaling
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