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Abstract: PO0340

Connecting Extracellular Vesicle Transfer RNA to Oxidative Stress in Injured Kidneys

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kwon, Sang-Ho, Augusta University Medical College of Georgia, Augusta, Georgia, United States
  • Lee, Byung Rho, Augusta University Medical College of Georgia, Augusta, Georgia, United States
Background

While urine-based liquid biopsy has recently expanded to the analyses of cell-free extracellular nucleic acid, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles as a new class of urine biomarkers for kidney injury has not been explored.

Methods

Using rat renal ischemia-reperfusion and tubular cell injury models, we tested if extracellular release of tRNA encapsulated in extracellular vesicles responds to kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles under oxidative stress.

Results

We detected a set of tRNAs present in urine that was packaged inside extracellular vesicles. We then identified extracellular vesicle-loaded tRNAs differentially released after ischemia-reperfusion injury and oxidative stress, in a reproducible manner. Next, we determined post-transcriptional methylation of these tRNA as a response to oxidative stress present in extracellular vesicle tRNAs. Mechanistically, oxidative stress decreases tRNAs loading into intracellular vesicles, mobilizes tRNAs to endosomes destined to extracellular vesicles, suppresses release of extracellular vesicles from the cell surface, and induces Maf1-mediated transcriptional repression of the tRNAs, all of which affect the availability of tRNAs in the cytoplasm.

Conclusion

Our data support that decreased release of non-fragmented tRNAs via extracellular vesicles reflects oxidative stress of kidney tubules, which might be a new source of urine biomarkers for ischemic kidney injury and could lead to rebalance protein translation in response to oxidative stress.

Funding

  • NIDDK Support