Kolb 2015 Abstract MiPschool Greenville 2015
|Hydrodynamic delivery for the treatment of acute kidney injury.|
Event: MiPschool Greenville 2015
Mitochondrial respiration is a critical process for normal kidney function. Kidneys that undergo an Acute Kidney Injury (AKI), specifically those injuries that result from ischemia, lead to changes in mitochondrial function and respiration. These changes in respiration are due to changes in TCA, Electron Transport Chain complexes, and regulation of ROS levels [1,2]. To study mitochondrial changes in the kidney as a result of an AKI a proteomic screen was conducted on kidneys two weeks after ischemic injury. The screen indicated that in response to an ischemic event there was an upregulation of proteins that may play a pivotal role in kidney recovery and subsequent protection from future ischemic events (Fig 1). One such protein, Isocitrate Dehydrogenase 2 (IDH2) plays an important role in the TCA and ROS clearance. Treatment of AKI is limited to supportive care, which was reported to cost patients approximately 10 billion dollars in 2012 . The limitations and cost of treatment lead to the idea of gene therapy as a possible means of treatment. However, delivering genes directly to the kidney and getting sufficient levels of expression has proven difficult. Recently a novel technique, hydrodynamic delivery, has shown promising results as a possible route of delivery for our genes . This technique uses pressure as a means to deliver genes, dyes, and vectors into the kidney (Fig 2). Our data indicates that hydrodynamic delivery of genes, such as IDH2, have the potential to protect mitochondria from ischemic injury and maintain normal mitochondrial function and physiology.
Labels: MiParea: Instruments;methods, mt-Medicine, Patients Pathology: Other Stress:Ischemia-reperfusion Organism: Human Tissue;cell: Kidney
1-IUPUI School Sc Dept Biology; 2-IUSM Dept Nephrology, Purdue Sc, Lafayette, IN, USA. - [email protected]
Figure 1. Proteomic Screen showing alterations in protein expression found in kidney mitochondria following IRI
Figure 2. Two photon image of the kidney following renal vein delivery of 150 Kd dextran and systemic delivery of Hoechst.
References and acknowledgements
- Brooks C, Wei Q, Cho SG, Dong Z (2009) Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. J Clin Invest 119:1275-85.
- Cruthirds DL, Novak L, Akhi KM, Sanders PW, Thompson JA, MacMillan-Crow LA (2003) Mitochondrial targets of oxidative stress during renal ischemia/reperfusion. Arch Biochem Biophys 412:27-33.
- Hofmann RM (2012) Preventing harm during treatment of acute kidney injury: what do we really know? Advances in chronic kidney disease 19:142-8.
- Corridon PR, Rhodes GJ, Leonard EC, Basile DP, Gattone VH 2nd, Bacallao RL, Atkinson SJ (2013) A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors. Am J Physiol Renal Physiol 304:F1217-29.