Abstract
Background: Renal ischemia/reperfusion (I/R) injury (RIRI) is the main cause of acute kidney injury (AKI) in patients. We investigated the role of miR-182 after renal ischemia/reperfusion (I/R) in rat to characterize the microRNA (miRNA) network activated during development and recovery from RIRI. Methods and Results: 12 h after lethal (45 min) renal ischemia, AKI was verified by renal histology (tubular necrosis and regeneration), blood urea nitrogen level, and renal mRNA expression in Wistar rats. We found that miR-182 markedly increased after renal I/R. In cell hypoxia/reoxygenation model, we found similar upregulation of miR-182. In function gain/loss assay, we confirmed an impaired effect of miR-182 and identified Forkhead box O3 (FoxO3) as a direct downstream target of it. By using miR-182 antagomir, the I/R injury was markedly ameliorated. Conclusions: Our results demonstrate that miR-182 promotes cell apoptosis and I/R injury through directly binding to FoxO3. The present study will provide potential therapeutic targets for renal I/R-induced AKI, and open a new avenue for AKI treatment by manipulating miRNAs levels.
Keywords:
miR-182,
Acute kidney injury,
Ischemia reperfusion injury,
FoxO3,
Apoptosis,
Proliferation
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