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Updated: Jul 31, 2025
Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction
Published on: May 7, 2015
Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming
Yalda Rahbar Saadat1, Seyed Mahdi Hosseiniyan Khatibi1, Anis Sani2
1Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
The kidneys are the most vulnerable organs to severe ischemic insult that results in cellular hypoxia under pathophysiological conditions. Large amounts of oxygen are consumed by the kidneys, mainly to produce energy for tubular reabsorption. Beyond high oxygen demand and the low oxygen supply, different other factors make kidneys vulnerable to ischemia which is deemed to be a major cause of acute kidney injury (AKI). On the other hand, kidneys are capable of sensing and responding to oxygen alternations to evade harms resulting from inadequate oxygen. The hypoxia-inducible factor (HIF) is the main conserved oxygen-sensing mechanism that maintains homeostasis under hypoxia through direct/indirect regulation of several genes that contribute to metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and so on. In response to oxygen availability, prolyl-hydroxylases (PHDs) control the HIF stability. This review focuses on the oxygen-sensing mechanisms in kidneys, particularly in proximal tubular cells (PTCs) and discusses the molecules involved in ischemic response and metabolic reprogramming. Moreover, the possible roles of non-coding RNAs (microRNAs and long non-coding RNAs) in the development of ischemic AKI are put forward.
Insights
Kidneys are vulnerable to acute kidney injury (AKI) from ischemia. Oxygen-sensing mechanisms, like hypoxia-inducible factor (HIF), help kidneys adapt to low oxygen levels.
Area of Science:
- Nephrology
- Molecular Biology
- Cellular Physiology
Background:
- Kidneys have high oxygen demand, making them susceptible to ischemic injury and acute kidney injury (AKI).
- Cellular hypoxia is a key factor in kidney damage.
- Kidneys possess intrinsic oxygen-sensing and response mechanisms to mitigate hypoxic harm.
Purpose of the Study:
- To review kidney oxygen-sensing mechanisms, focusing on proximal tubular cells (PTCs).
- To discuss molecules involved in the ischemic response and metabolic reprogramming in kidneys.
- To explore the role of non-coding RNAs in ischemic AKI development.
Main Methods:
- Literature review focusing on kidney physiology and hypoxia.
- Analysis of oxygen-sensing pathways, particularly the hypoxia-inducible factor (HIF) pathway.
- Discussion of molecular regulators like prolyl-hydroxylases (PHDs) and non-coding RNAs.
Main Results:
- The hypoxia-inducible factor (HIF) is a central oxygen sensor crucial for maintaining homeostasis under hypoxia.
- PHDs regulate HIF stability in response to oxygen availability.
- Non-coding RNAs may play a significant role in the pathogenesis of ischemic AKI.
Conclusions:
- Understanding kidney oxygen-sensing mechanisms is vital for addressing ischemic AKI.
- HIF and its regulators are key players in kidney adaptation to hypoxia.
- Non-coding RNAs represent a potential therapeutic target for ischemic kidney injury.
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