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Updated: Dec 7, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
Jean-Paul Decuypere1,2, Shawn Hutchinson1,2, Diethard Monbaliu1,2
1Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology and Immunology, KU Leuven, B-3000 Leuven, Belgium.
Abstract:
Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However, autophagy is also suggested to enhance cell death when the ischemic burden is too strong. To investigate whether the role of autophagy depends on the severity of ischemic stress, we analyzed the dynamics of autophagy and apoptosis in an IR rat model with mild (45 min) or severe (60 min) renal ischemia. Following mild IR, renal injury was associated with reduced autophagy, enhanced mammalian target of rapamycin (mTOR) activity, and apoptosis. Severe IR, on the other hand, was associated with a higher autophagic activity, independent of mTOR, and without affecting apoptosis. Autophagy stimulation by trehalose injected 24 and 48 h prior to onset of severe ischemia did not reduce renal injury markers nor function, but reduced apoptosis and restored tubular dilation 7 days post reperfusion. This suggests that trehalose-dependent autophagy stimulation enhances tissue repair following an IR injury. Our data show that autophagy dynamics are strongly dependent on the severity of IR and that trehalose shows the potential to trigger autophagy-dependent repair processes following renal IR injury.
Insights
Autophagy
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Renal ischemia-reperfusion (IR) injury is a primary cause of acute kidney injury.
- Autophagy, a cellular degradation process, plays a complex role in cell death and survival during IR.
- The severity of ischemic stress may influence autophagy's protective or detrimental effects.
Purpose of the Study:
- To investigate the role of autophagy in renal IR injury based on the severity of ischemia.
- To analyze the dynamics of autophagy and apoptosis in response to mild and severe IR.
- To evaluate the therapeutic potential of trehalose in modulating autophagy and mitigating IR injury.
Main Methods:
- Establishment of a rat model for renal IR injury with varying durations (45 min mild, 60 min severe).
- Analysis of autophagy markers, mammalian target of rapamycin (mTOR) activity, and apoptosis.
- Administration of trehalose prior to severe IR to assess its impact on injury and repair.
Main Results:
- Mild IR led to reduced autophagy, increased mTOR activity, and apoptosis.
- Severe IR showed increased autophagy independent of mTOR, with no significant apoptosis.
- Trehalose treatment in severe IR reduced apoptosis and improved tubular dilation, but did not alter overall injury markers or function.
Conclusions:
- Autophagy dynamics are critically dependent on the severity of renal IR.
- Trehalose-mediated autophagy stimulation shows potential for promoting tissue repair post-IR injury.
- Targeting autophagy may offer a therapeutic strategy for acute kidney injury, with outcomes varying by injury severity.
