Kidney Week

Abstract: FR-PO081

UCP2-Dependent Improvement of Mitochondrial Dynamics Preserves AKI

Session Information

• AKI: Tubules, Metabolism, New Models
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Zhou, Yang, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China

Yang Zhou,

• Qin, Nan, Nanjing Medical University, Nanjing, JIANGSU , China

Nan Qin,

• Mao, Xiaoming, Nanjing Medical University, Nanjing, JIANGSU , China

Xiaoming Mao,

• Yang, Junwei, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China

Junwei Yang,

Background

Acute kidney injury (AKI) is a public health concern with high morbidity and mortality rate in hospitalized patients and the survivors have 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.

Methods

AKI was induced by ischemia/reperfusion injury. We generated proximal tubular cells specific uncoupling protein 2 (UCP2) knockout mice to investigate the role of UCP2 on AKI. Primary tubular epithelial cells were cultured under normoxia or hypoxia conditions. Mitochondrial dynamics were evaluated by electron microscopy, western blot analysis and immunofluorescent staining.

Results

Here, in murine ischemia/reperfusion-induced (I/R-induced) AKI model, we determined that mitochondrial damage is associated with the level of renal 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 suffered I/R injury experienced more severe AKI and mitochondrial fragmentation than wild-type (WT) mice. Moreover, Genetic or pharmacologic 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 Ucp2^-/- cells, while increase of UCP2 improved hypoxia-induced disturbance between mitochondrial fusion and fission. Furthermore, modulation of UCP2 suggested its role in preserving mitochondrial integrity by preventing loss of membrane potential and reducing subsequent mitophagy.

Conclusion

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.

Funding

• Government Support - Non-U.S.