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Published on: June 2, 2015
Molecular mechanisms of ischemic preconditioning in the kidney
Pinelopi P Kapitsinou1, Volker H Haase2
1Departments of Medicine, Anatomy and Cell Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; pkapitsinou@kumc.edu.
Abstract:
More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.
Insights
Hypoxia-inducible factors (HIFs) are key to preconditioning, protecting kidneys from ischemic injury by regulating cellular metabolism and protective responses. Activating HIFs offers therapeutic potential for preventing and treating acute kidney injury.
Area of Science:
- Nephrology
- Cellular and Molecular Medicine
Background:
- Acute kidney injury (AKI) presents significant morbidity and mortality.
- Ischemic events account for most AKI cases, necessitating improved therapeutic strategies.
- Ischemic preconditioning can attenuate kidney susceptibility to injury.
Purpose of the Study:
- To review oxygen-regulated cellular and molecular responses in renal protection.
- To focus on hypoxia-inducible factors (HIFs) in ischemic/hypoxic preconditioning.
- To critically examine the therapeutic potential of HIF activation for ischemic kidney injury.
Main Methods:
- Literature review focusing on oxygen-regulated pathways in kidney injury.
- Analysis of the role of HIFs in cellular adaptation to hypoxia.
- Examination of signaling pathways coordinated by HIFs.
Main Results:
- HIFs are central mediators of cellular adaptation to hypoxia.
- HIFs reprogram cellular energy metabolism during preconditioning.
- HIFs coordinate multiple protective responses including antiapoptotic and anti-oxidative stress mechanisms.
Conclusions:
- HIFs play a crucial role in the renoprotective effects of ischemic/hypoxic preconditioning.
- HIF activation holds therapeutic promise for preventing and treating ischemic AKI.
- Further research into HIF activation is warranted for clinical applications in AKI.
