Abstract: SA-PO0022
Muscle-Kidney Crosstalk Confers Renoprotection via MG53-Containing Extracellular Vesicles
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Lin, Pei-Hui, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Duann, Pu, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Li, Haichang, The Ohio State University, Columbus, Ohio, United States
- Zhang, Min, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Group or Team Name
- OSUMC-Lin
Background
Myokines, the physiological mediators secreted by skeletal muscle, may modulate kidney function during acute injury or chronic kidney disease. We previously showed that MG53, a muscle-predominant protein, confers kidney protection in the face of ischemia-reperfusion (I/R) acute kidney injury (AKI) and unilateral ureteral obstruction (UUO)-mediated kidney fibrosis. In this, we explored if limb remote ischemic preconditioning (RIPC) protects the kidney against I/R-AKI via elevation of MG53-containing extracellular vesicles (MG53-EVs). For translational purposes, we generated MG53-EVs from cells overexpressing MG53 and measured their effects on kidney function in vivo and in vitro effects.
Methods
We measured systemic exosomal MG53 and kidney MG53 levels during the acute phase (2-hours) with or without RIPC before I/R-AKI; kidney function, injury pathology and apoptosis at 48-hours post injury were evaluated. We further characterized kidney phenotypes of mg53-/- mice with function (SCr, UPCR) and structural (transmission EM) analyses. We characterized MG53-EVs derived from C2C12 myotubes and engineered NIH3T3 cells overexpressing MG53. We measured MG53-EVs acute recruitment to injured kidney. We injected engineered MG53-EVs into mg53-/- mice and measured kidney-targeting effects, sustainability and function. We also measured MG53-EVs uptake by kidney proximal tubule cells in vitro.
Results
When applied before AKI, RIPC released mediators reduced cell death, but did not affect functional (SCr) or structural (injury scores) impairment up to 48-hr post-injury. In mg53-/- mice, we found an intrinsic glomerular structural defect of thickening GBM and heightened UPAC. In vivo, bioengineered MG53-EVs were quickly recruited (within 1-hr) to the injured kidney proximal tubules. Using a chronic multiple injection regimen into mg53-/- mice, MG53-EVs were retained in kidney (tubules and glomeruli) and attenuated kidney functional defects in mg53-/- mice after 28 days. In vitro, MG53-EVs modified intracellular AKT signaling, enhanced PTE survival during oxidative stress damage.
Conclusion
MG53 is a powerful endogenous protective factor; MG53 EVs are myokines and carry functional protein and genetic information that facilitate sustained crosstalk between muscle and kidney and attenuates kidney damage. Engineered MG53-EVs have potential to serve as a nano-regenerative medicine to mitigate kidney dysfunction.
Acknowledgment
NIH R01-DK106394,
R01-AG062896,
R21-AI166273
intramural OSU research fund
Funding
- NIDDK Support