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.
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This work was supported by the Kidney Research Center at Tabriz University of Medical Sciences, Tabriz, Iran (Grant # 71526).
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MA and SZV designed the article. YRS, SMHKh, and AS wrote the manuscript. SZV and MA revised the manuscript. All authors read and approved the final manuscript.
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Rahbar Saadat, Y., Hosseiniyan Khatibi, S.M., Sani, A. et al. Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming. Inflammopharmacol 31, 1657–1669 (2023). https://doi.org/10.1007/s10787-023-01232-x
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DOI: https://doi.org/10.1007/s10787-023-01232-x