Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases

Da Wei Lin, Yung Chien Hsu*, Cheng Chih Chang, Ching Chuan Hsieh, Chun Liang Lin*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all are related to reduction-oxidation (redox). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor targeting many antioxidant genes. In non-stressed conditions, NRF2 maintains the hemostasis of redox with housekeeping work. It expresses constitutively with basal activity, maintained by Kelch-like-ECH-associated protein 1 (KEAP1)-associated ubiquitination and degradation. When encountering stress, it can be up-regulated by several mechanisms to exert its anti-oxidative ability in diseases or inflammatory processes to protect tissues and organs from further damage. From acute kidney injury to chronic kidney diseases, such as diabetic nephropathy or glomerular disease, many results of studies have suggested that, as a master of regulating redox, NRF2 is a therapeutic option. It was not until the early termination of the clinical phase 3 trial of diabetic nephropathy due to heart failure as an unexpected side effect that we renewed our understanding of NRF2. NRF2 is not just a simple antioxidant capacity but has pleiotropic activities, harmful or helpful, depending on the conditions and backgrounds.

Original languageEnglish
Article number6053
JournalInternational Journal of Molecular Sciences
Volume24
Issue number7
DOIs
StatePublished - 23 03 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • acute kidney injury (AKI)
  • chronic kidney disease (CKD)
  • diabetes nephropathy
  • nuclear factor erythroid 2-related factor 2 (NRF2)
  • reactive oxygen species (ROS)
  • reduction-oxidation (redox)
  • Reactive Oxygen Species/metabolism
  • Antioxidants/therapeutic use
  • Oxidative Stress
  • Humans
  • Diabetic Nephropathies/metabolism
  • Kelch-Like ECH-Associated Protein 1/metabolism
  • Kidney/metabolism
  • NF-E2-Related Factor 2/metabolism

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