Identification of urinary microRNA biomarkers for in vivo gentamicin-induced nephrotoxicity models

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

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.

Keywords: Acute kidney injury; biomarker; gentamicin; microRNAs; nephrotoxicity.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Animals
  • Anti-Bacterial Agents / toxicity*
  • Biomarkers / urine
  • Disease Models, Animal*
  • Female
  • Gentamicins / toxicity*
  • MicroRNAs / urine*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Bacterial Agents
  • Biomarkers
  • Gentamicins
  • MicroRNAs