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Updated: Feb 2, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
UCP2-dependent improvement of mitochondrial dynamics protects against acute kidney injury
Nan Qin1, Ting Cai1, Qingqing Ke1
1Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
Abstract:
Acute kidney injury (AKI) is a public health concern, with high morbidity and mortality rates in hospitalized patients and because survivors have an increased risk of progression to chronic kidney disease. Mitochondrial damage is the critical driver of AKI-associated dysfunction and loss of tubular epithelial cells; however, the pathways that mediate these events are poorly defined. Here, in murine ischemia/reperfusion (I/R)-induced AKI, we determined that mitochondrial damage is associated with the level of renal uncoupling protein 2 (UCP2). In hypoxia-damaged proximal tubular cells, a disruption of mitochondrial dynamics demonstrated by mitochondrial fragmentation and disturbance between fusion and fission was clearly indicated. Ucp2-deficient mice (knockout mice) with I/R injury experienced more severe AKI and mitochondrial fragmentation than wild-type mice. Moreover, genetic or pharmacological treatment increased UCP2 expression, improved renal function, reduced tubular injury and limited mitochondrial fission. In cultured proximal tubular epithelial cells, hypoxia-induced mitochondrial fission was exacerbated in cells with UCP2 deletion, whereas an increase in UCP2 ameliorated the hypoxia-induced disturbance of the balance between mitochondrial fusion and fission. Furthermore, results following modulation of UCP2 suggested it has a role in preserving mitochondrial integrity by preventing loss of membrane potential and reducing subsequent mitophagy. Taken together, our results indicate that UCP2 is protective against AKI and suggest that enhancing UCP2 to improve mitochondrial dynamics has potential as a strategy for improving outcomes of renal injury. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Insights
Uncoupling protein 2 (UCP2) protects against acute kidney injury (AKI) by maintaining mitochondrial integrity. Enhancing UCP2 may improve outcomes for patients with renal injury.
Area of Science:
- Nephrology
- Mitochondrial Biology
- Cellular Physiology
Background:
- Acute kidney injury (AKI) is a significant health issue with high mortality.
- Mitochondrial damage is a key factor in AKI, but the underlying mechanisms are not fully understood.
- The role of uncoupling protein 2 (UCP2) in AKI pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the role of UCP2 in murine ischemia/reperfusion (I/R)-induced AKI.
- To determine if UCP2 influences mitochondrial dynamics and integrity in kidney injury.
- To explore UCP2 as a potential therapeutic target for AKI.
Main Methods:
- Utilized a murine model of ischemia/reperfusion (I/R)-induced AKI.
- Compared AKI severity and mitochondrial fragmentation in UCP2-deficient (knockout) mice and wild-type mice.
- Assessed the effects of genetic or pharmacological UCP2 modulation on renal function and tubular injury.
- Examined mitochondrial dynamics (fusion/fission balance) in cultured proximal tubular epithelial cells under hypoxic conditions with varying UCP2 levels.
Main Results:
- UCP2-deficient mice exhibited more severe AKI and mitochondrial fragmentation after I/R injury compared to wild-type mice.
- Increased UCP2 expression (via genetic or pharmacological means) improved renal function, reduced tubular injury, and limited mitochondrial fission.
- In cultured cells, UCP2 deletion exacerbated hypoxia-induced mitochondrial fission, while UCP2 upregulation ameliorated this disturbance.
- UCP2 was found to preserve mitochondrial integrity by maintaining membrane potential and reducing mitophagy.
Conclusions:
- UCP2 plays a protective role in mitigating acute kidney injury.
- UCP2 is crucial for maintaining mitochondrial dynamics and integrity during renal injury.
- Enhancing UCP2 expression presents a promising therapeutic strategy for improving outcomes in AKI.
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