# Myokine function of MG53 in muscle injury-repair and regeneration

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $352,683

## Abstract

SUMMARY
Skeletal muscle injury-repair and regeneration is a multi-cellular process that involves repair of acute injury to
the sarcolemma, mobilization of satellite cells to replace the lost-muscle fibers, and control of fibrotic
remodeling for maintenance of muscle integrity. In muscular dystrophy, compromised sarcolemma integrity or
membrane repair triggers the cascade of muscle degeneration that incurs progressive, severe morbidity and
ultimately mortality. Developing therapeutic approaches to improve sarcolemma integrity while facilitating
regeneration of injured muscle fibers remain a major challenge in muscle physiology research. This project
builds on the discovery of MG53, a member of the TRIM-family protein, as an essential component of the cell
membrane repair machinery. MG53 functions in vesicle trafficking and facilitates the nucleation of intracellular
vesicles to sites of membrane disruption for repair patch formation. Native MG53 is present in blood circulation,
at levels directly correlating with injury or secretory activity of the muscle. Administration of recombinant human
MG53 (rhMG53) protein protects muscle fibers and stem cells from injury, and reduces muscle fibrosis in the
mdx mouse model. Our research with MG53 over the past few years has established a potential tri-functional
role for MG53 in muscle injury-regeneration, as a facilitator to repair acute sarcolemma injury, a contributor to
activate satellite cells during the early phase of muscle injury, and a modulator of fibrosis by controlling
fibroblast differentiation associated with chronic muscle injury. We envision that targeting the tri-functional role
of MG53 will have advantage over the current paradigms for treating muscular dystrophy. In Aim 1, we will
determine the pathways that transduce the newly identified myokine function of MG53 into activation of satellite
cells in response to acute muscle injury; define the mechanisms that underlie MG53’s function in regulating
fibrosis during chronic muscle injury; and test if non-invasive interventions can modulate circulating MG53
levels toward muscle injury-regeneration. If circulating MG53 plays a role in satellite cell activation, we predict
that ischemia-preconditioning that releases MG53 without muscle injury, or inducible secretion of MG53 from a
transgenic mouse model, will effectively activate satellite cells and muscle regeneration following injury. In Aim
2, we will evaluate the safety and efficacy for sustained elevation of MG53 in circulation to preserve muscle
integrity/satellite cell activation/fibrosis control in animal models of muscular dystrophy. Fulfillment of the
studies in this project will advance the biology of MG53 in muscle injury-repair and regeneration, and lay the
foundation for our translational approach for targeting MG53 function for treatment of muscular dystrophy.

## Key facts

- **NIH application ID:** 9924247
- **Project number:** 5R01AR070752-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jianjie Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,683
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924247

## Citation

> US National Institutes of Health, RePORTER application 9924247, Myokine function of MG53 in muscle injury-repair and regeneration (5R01AR070752-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9924247. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*