MicroRNA-125b as a new potential biomarker on diagnosis of renal ischemia-reperfusion injury

J Surg Res. 2017 Jan:207:241-248. doi: 10.1016/j.jss.2016.08.067. Epub 2016 Aug 27.

Abstract

Background: Acute renal failure is commonly seen in the perioperative period. Ischemia-reperfusion (IR) injury plays a major role in acute renal failure and delayed graft function. MicroRNAs (miRs), which are pivotal modulators of cell activities, offer a major opportunity for affective diagnosis and treatment strategies because they are tissue specific and in the center of gene expression modulation. The effect of bardoxolone methyl (BM) on miR-21, miR-223-5p, and miR-125b in renal IR injury was evaluated in this study.

Methods: Wistar-Albino rats (12-16 wk old, weighing 300-350 g) were used in the study. Rats (n = 6) were randomized into three groups (control, IR, and BM + IR). Tissue levels of miRs were analyzed with reverse transcription polymerase chain reaction.

Results: Significant reduction of urea and total oxidant status, increase of total antioxidant status, and oxidative stress index were identified in the IR + BM group compared with the IR group. Significant increases of miR-21 (2842.82-fold) and miR-125b (536.8-fold) were identified in the IR group compared with the control group; however, miR-223-5p levels did not show any significant difference. Also, miR-21 and miR-125b were significantly reduced in the IR + BM group compared with the IR group. Reduced histopathologic changes were observed in the IR + BM group. A significant decrease in the number of tunel-positive cells was identified in the IR + BM group compared with the IR group.

Conclusions: miR-125b was significantly increased in IR injury; thus, miR-125b can be a potential novel marker that can be used in diagnosis and treatment of renal IR injury. BM reduces miR-21 and miR-125b in case of IR injury and makes functional and histopathologic repairs.

Keywords: Bardoxolone methyl; CDDO-Me; MicroRNAs; Renal ischemia–reperfusion injury; miR-125b; miR-21; miR-223-5p.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Biomarkers / metabolism
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • MicroRNAs / metabolism*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / therapeutic use
  • Oxidative Stress / drug effects
  • Random Allocation
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reperfusion Injury / diagnosis*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology

Substances

  • Antioxidants
  • Biomarkers
  • MIRN125 microRNA, rat
  • MIRN223 microRNA, rat
  • MicroRNAs
  • mirn21 microRNA, rat
  • Oleanolic Acid
  • bardoxolone methyl