J Vet Sci.  2020 Nov;21(6):e81. 10.4142/jvs.2020.21.e81.

Identification of urinary microRNA biomarkers for in vivo gentamicininduced nephrotoxicity models

Affiliations
  • 1Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea
  • 2Animal Pathodiagnostic Laboratory, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea
  • 3Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea

Abstract

Background
Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers.
Objectives
In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity.
Methods
For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats.
Results
GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein.
Conclusions
These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

Keyword

Acute kidney injury; biomarker; gentamicin; microRNAs; nephrotoxicity
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