Activation of the miR-17 family and miR-21 during murine kidney ischemia-reperfusion injury

Nucleic Acid Ther. 2013 Oct;23(5):344-54. doi: 10.1089/nat.2013.0438.

Abstract

Background: Ischemia-reperfusion (I/R) is the main cause of acute kidney injury (AKI) in patients. We investigated renal microRNA (miRNA) expression profiles and the time course of changes in selected miRNA expressions after renal I/R to characterize the miRNA network activated during development and recovery from AKI.

Methods and results: One day after lethal (30 minutes) and sublethal (20 minutes) renal ischemia, AKI was verified by renal histology (tubular necrosis, regeneration), blood urea nitrogen (BUN) level, renal mRNA expression, and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL) in C57BL/6J mice. On the first day after 30-minute, lethal I/R miR-21, miR-17-5p, and miR-106a were elevated out of the 21 miRNAs successfully profiled on the Luminex multiplex assay. After 20-minute, sublethal I/R, renal miR-17-5p and miR-106a expressions were elevated on the first and second days of reperfusion, while miR-21 expression increased later and lasted longer. Renal miR-17-5p and miR-21 expressions correlated with each other. Renal function returned to normal on the fourth day after sublethal I/R.

Conclusions: Our results demonstrate that besides miR-21, miR-17-5p, and miR-106a are additionally activated during the maintenance and recovery phases of renal I/R injury. Furthermore, a correlation between renal miR-17-5p and miR-21 expressions warrants further investigation of how they may influence each other and the outcome of renal ischemia-reperfusion injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute-Phase Proteins / genetics
  • Animals
  • Blood Urea Nitrogen
  • Gene Expression Regulation
  • Kidney / metabolism
  • Kidney / pathology
  • Lipocalin-2
  • Lipocalins / blood
  • Lipocalins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oncogene Proteins / blood
  • Oncogene Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reperfusion Injury / complications
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology

Substances

  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Mirn106 microRNA, mouse
  • Mirn17 microRNA, mouse
  • Oncogene Proteins
  • RNA, Messenger
  • Lcn2 protein, mouse