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Abstract: PO2228

Analysis of Urinary Exosomal RNAs After Treatment of Rats with an Nrf2 Activator

Session Information

Category: Pathology and Lab Medicine

  • 1601 Pathology and Lab Medicine: Basic

Authors

  • Tanaka, Ayae, Veterinary Pharmacology, University of Miyazaki, Miyazaki, Miyazaki, Japan
  • Sonoda, Hiroko, Veterinary Pharmacology, University of Miyazaki, Miyazaki, Miyazaki, Japan
  • Sakaguchi, Yui, Veterinary Pharmacology, University of Miyazaki, Miyazaki, Miyazaki, Japan
  • Ikeda, Masahiro, Veterinary Pharmacology, University of Miyazaki, Miyazaki, Miyazaki, Japan
Background

Renal NF-E2-related-factor 2 (Nrf2) is known to be increased in the presence of oxidative stress. Administration of an Nrf2 activator has also been reported to lessen the degree of renal damage. However, biomarkers for detection of Nrf2 activation in the kidney are largely unknown. Urinary exosomes, a subset of extracellular vesicles released by renal epithelial cells, contain RNA molecules that are expected to be biomarkers for renal disease. Thus we analyzed urinary exosomal RNAs after administration of bardoxolone methyl (BARD), an Nrf2 activator, in rats.

Methods

Male Sprague-Dawley rats were randomly divided into two groups; the BARD group, intraperitoneally receiving 10 mg/kg BARD, and the control group, receiving only vehicle (100% DMSO). The urine was obtained for 6 hours just after administration, and exosomes were isolated from the urine. At 6 hours after administration, rats were sacrificed and the kidneys were removed. Thereafter RNAs were extracted from the kidneys and urinary exosomes. The RNAs (27,012 mRNAs amd 1,218 miRNAs) were analyzed with microarrays.

Results

BARD altered expression of 98 renal mRNAs and 357 urinary exosomal mRNAs with more than 2.0-fold relative to the control. BARD also changed expression of 15 renal miRNAs and 3 urinary exosomal miRNAs. The correlation coefficients between renal and urinary exosomal mRNAs as well as miRNAs were both less than 0.1. mRNAs that were commonly changed in both the kidney and urinary exosomes were 13. Among them, 8 genes are known to be targets of Nrf2 including Akr1b8, Akr1c19, Bach1, Ephx1, Hmox1, Pir, Slc40a1 and Ugdh. Of 8 genes, Akr1b8 and Pir were increased more than 10-fold in the kidney and more than 4.0-fold in urinary exosomes. For miRNA, only rno-miR-877 was changed in both the kidney and urinary exosomes.

Conclusion

The correlation coefficients between renal and exosomal RNAs were less than 0.1, suggesting that specific RNAs were selectively loaded into exosomes. In addition, Akr1b8 and Pir expression was dramatically increased in both kidney and urinary exosomes. Therefore, they could be potential biomarkers to detect their renal expression changes by renal Nrf2 activation.