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Updated: Jul 23, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
MiR-132-3p activation aggravates renal ischemia-reperfusion injury by targeting Sirt1/PGC1alpha axis
Chenglong Li1, Shangting Han2, Jiefu Zhu2
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Abstract:
The pathogenesis of renal ischemic diseases remains unclear. In this study, we demonstrate the induction of microRNA-132-3p (miR-132-3p) in ischemic acute kidney injury (AKI) and cultured renal tubular cells under oxidative stress. miR-132-3p mimic increased apoptosis in renal tubular cells and enhanced ischemic AKI in mice, whereas miR-132-3p inhibition offered protective effects. We analyzed miR-132-3p target genes through bioinformatic analysis and Sirt1 was predicted as the target gene of miR-132-3p. Luciferase microRNA target reporter assay further verified Sirt1 as a direct target of miR-132-3p. In cultured tubular cells and mouse kidneys, IRI and H2O2 treatment repressed Sirt1 and PGC-1α/NRF2/HO-1 expression, whereas anti-miR-132-3p preserved Sirt1 and PGC-1α/NRF2/HO-1 expression. In renal tubular, Sirt1 inhibitor suppressed PGC1-1α/NRF2/HO-1 expression and aggravated tubular apoptosis. Together, the results suggest that miR-132-3p induction aggravates ischemic AKI and oxidative stress by repressing Sirt1 expression, and miR-132-3p inhibition offers renal protection and may be a potential therapeutic target.
Insights
microRNA-132-3p (miR-132-3p) worsens kidney injury and oxidative stress by targeting Sirt1. Inhibiting miR-132-3p protects kidneys, suggesting it as a therapeutic target for ischemic acute kidney injury (AKI).
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- The exact mechanisms behind renal ischemic diseases are not fully understood.
- Oxidative stress plays a significant role in the development of acute kidney injury (AKI).
Purpose of the Study:
- To investigate the role of microRNA-132-3p (miR-132-3p) in the pathogenesis of ischemic AKI.
- To identify miR-132-3p targets and elucidate its mechanism of action in renal injury.
Main Methods:
- Induction of miR-132-3p in renal tubular cells and mouse models of ischemic AKI.
- Bioinformatic analysis and luciferase reporter assays to identify miR-132-3p targets.
- Assessment of apoptosis, Sirt1, and PGC-1α/NRF2/HO-1 pathway expression.
Main Results:
- miR-132-3p was induced in ischemic AKI and oxidative stress conditions.
- miR-132-3p mimic exacerbated renal tubular cell apoptosis and ischemic AKI.
- Sirt1 was identified as a direct target of miR-132-3p; its repression by miR-132-3p led to suppressed PGC-1α/NRF2/HO-1 and increased apoptosis.
Conclusions:
- miR-132-3p aggravates ischemic AKI and oxidative stress by inhibiting Sirt1 expression.
- Inhibition of miR-132-3p demonstrates renal protective effects.
- miR-132-3p inhibition represents a potential therapeutic strategy for ischemic AKI.
