Abstract: TH-PO0109
MG53 in Sepsis-Induced AKI: Underlying Mechanisms for Renoprotection
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Zhang, Min, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Duann, Pu, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Lin, Pei-Hui, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Group or Team Name
- Lin Lab.
Background
MG53 (TRIM72) is a muscle-predominant protein and functions as a circulating myokine that appears to confer tissue protection. We previously showed that MG53 confers kidney protection in the face of ischemia-reperfusion (I/R) kidney injury and unilateral ureteral obstruction (UUO)-mediated kidney fibrosis. Compared to wild type littermates, kidneys of mg53-/- mice have increased F4/80+ and CD11b+ myeloid cell infiltration (from 4 - 5 months age) and develop age-dependent kidney fibrosis. Infiltration of these myeloid cells or sustained activation of kidney resident immune cells may contribute to this exacerbated fibrosis and/or impact recovery from acute kidney injury. In the present study, we explored the potential involvement of MG53 in sepsis-induced AKI (SI-AKI), a model with severe renal dysfunction and high mortality rate.
Methods
We generated the mouse strain TRE-STOPflox-tPA-MG53 (ctPA-MG53) for conditional MG53 over-expression. This mouse strain was bred to LysMcre (myeloid expression) to induce doxycycline (DOX)-dependent conditional myeloid MG53-overexpression. We utilized a cecal ligation and perforation (CLP) animal model as SI-AKI to study the in vivo physiological role of elevated MG53 in myeloid cells on renoprotection and immune cell-kidney crosstalk associated with SI-AKI. We also isolated bone marrow derived macrophage (BMDM) for in vitro functional verification.
Results
We confirmed the elevated serum and excessive myeloid-specific MG53 expression from our conditional myeloid-specific transgenic mice. Transgenic LysMcre; ctPAMG53 mice exhibited reduced F4/80+ macrophage infiltration compared to control mice and had improved kidney function (BUN assay) and reduced kidney injury (NGAL, Kim1) after SI-AKI. We also observed the expression level of MG53 changed from transgenic mice upon BMDM In vitro M1 and M2 polarization assay.
Conclusion
We have established an in vivo animal system to study the impact of myeloid and circulating MG53 in SI-AKI. Elevated MG53 conferred renoprotection with functional improvement and reduced kidney injury. We also established an in vitro system to investigate the influence of MG53 on BMDM polarization.
Funding
- Other NIH Support