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Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
MiR-182 Promotes Ischemia/Reperfusion-Induced Acute Kidney Injury in Rat by Targeting FoxO3
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
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.
Insights
MicroRNA-182 (miR-182) exacerbates renal ischemia/reperfusion (I/R) injury by targeting FoxO3. Inhibiting miR-182 offers a potential therapeutic strategy for acute kidney injury (AKI).
Area of Science:
- Molecular Biology
- Renal Physiology
- MicroRNA Therapeutics
Background:
- Renal ischemia/reperfusion (I/R) injury is a primary cause of acute kidney injury (AKI).
- Understanding the microRNA (miRNA) network in RIRI is crucial for developing new treatments.
Purpose of the Study:
- To investigate the role of miR-182 in renal I/R injury.
- To characterize the miRNA network activated during RIRI.
Main Methods:
- Induction of renal I/R injury in Wistar rats.
- Assessment of AKI using histology, blood urea nitrogen, and mRNA expression.
- In vitro cell hypoxia/reoxygenation model.
- MiRNA gain/loss function assays and target identification (FoxO3).
- Administration of miR-182 antagomir.
Main Results:
- miR-182 expression significantly increased following renal I/R and in a cell hypoxia/reoxygenation model.
- miR-182 was confirmed to directly target Forkhead box O3 (FoxO3).
- Inhibition of miR-182 using an antagomir markedly ameliorated I/R injury.
Conclusions:
- miR-182 promotes apoptosis and exacerbates renal I/R injury by targeting FoxO3.
- Targeting miR-182 presents a potential therapeutic avenue for AKI.
- Manipulation of miRNA levels offers a novel strategy for AKI treatment.
