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Abstract: PO0624

TRIM72-Containing Exosome for Kidney-Targeted Expression and Protection

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Duann, Pu, The Ohio State University, Columbus, Ohio, United States
  • Li, Haichang, The Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., The Ohio State University, Columbus, Ohio, United States
  • Lin, Pei-hui, The Ohio State University, Columbus, Ohio, United States
Background

TRIM72 is a myokine and appears to confer protection to the kidney in ischemia-reperfusion (I/R) injury. There are low levels in the kidney. We did experiments to see if TRIM72 could be transferred to the kidney so it could be used therapeutically.

Methods

Exosomes were purified from C2C12 myotubes differentiated from C2C12 myoblasts by differential centrifugation. C2C12 exosomes were given to TRIM72 null mice twice weekly for 4-weeks by tail-vein injection. Five-days post the last exosome injection, real time PCR and western blotting were used to examine tissue expression. For comparison, samples obtained from wildtype littermates served as positive controls.

Results

TRIM72 mRNA remained detectable five days post the final C2C12 exosome infusion. Moreover, TRIM72 mRNA delivered by exosomes reconstituted TRIM72 to the same organ distribution as in wildtype littermates, with high levels in kidney, skeletal muscle and moderate levels in heart and skin. TRIM72 protein expression was detected in tissues accordingly to TRIM72 mRNA distribution. Compared to a TRIM72-deficient exosome derived from NIH3T3 condition media, treatment with C2C12 exosome mitigated high serum creatinine level of I/R injured wildtype mice. This suggested a sustained TRIM72 expression and protection in kidney when delivered in exosome format.

Conclusion

Adoptive transfer of C2C12 exosomes demonstrated TRIM72 could be reconstituted to its native organ distribution and expression in TRIM72-deficient mice. TRIM72-containing exosome mitigated elevated serum creatinine level of I/R injured mice. Pharmacologic administration of TRIM72-containing exosome might be a promising approach for the treatment of kidney disease.

Funding

  • NIDDK Support