Recombinant MG53 Protein Modulates Therapeutic Cell Membrane Repair in Treatment of Muscular Dystrophy

Abstract

Recombinant human MG53 protein can increase membrane repair after injury in cells and can reduce pathology in animal models of muscle injury and muscular dystrophy.

Modulation of Wound Healing and Scar Formation by MG53 Protein-mediated Cell Membrane Repair

“…3a, right panel, in response to injury caused by penetration of a microelectrode into the plasma membrane, GFP-MG53 rapidly translocated toward the acute injury site. This GFP-MG53 translocation to membrane injury sites in keratinocytes is similar to that observed in C2C12, HEK293, and other cell types (14,18).…”

“…rhMG53 protein was purified from Escherichia coli fermentation as described previously (18). rhMG53 was stored as lyophilized powder and dissolved in saline solution or encapsulated in hydrogel before use.…”

“…50 l of supernatant was transferred from the well to a new 96-well plate for a lactate dehydrogenase release assay with a lactate dehydrogenase cytotoxicity detection kit (Thermo Scientific). Measurement of the release of lactate dehydrogenase following microglass bead damage was used as an index of membrane injury (18,23). The released lactate dehydrogenase was calculated by subtracting the basal lactate dehydrogenase release from wells without glass beads (no damage) from the experimental conditions.…”

“…MG53 knockout mice (mg53 Ϫ/Ϫ ) exhibit defective membrane repair in striated muscle that leads to progressive skeletal myopathy and increased vulnerability of cardiomyocytes to ischemia-reperfusion-induced injury (14,16,17). Moreover, the recombinant human MG53 (rhMG53) protein can protect various cell types against membrane disruption when applied to the extracellular environment and ameliorate the pathology associated with muscular dystrophy and lung injury (18,19). We have also shown that rhMG53 is effective in protection against myocardial infarction (20) and acute kidney injury (21).…”

S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells

“…Poor plasma membrane repair (PMR) is also associated with NiemannPick type A, 7 diabetes, 8 and ChediakHigashi 9 syndrome and therapies targeting PMR have been shown to be effective in treating muscle and lung injuries. [10][11][12] While much of the focus has been on disease resulting from poor PMR, we have recently identified that improved PMR is an important contributor for cancer metastasis. 13 Human breast cancer cells that turn metastatic through Keywords: actin, annexins, Annexin A2, breast cancer, cancer, plasma membrane repair, S100 proteins, S100A11, Metastasis up-regulation of truncated EGF receptor (ErbB2) also need to up-regulate their PMR machinery, and absence of enhanced PMR compromises their invasive ability.…”