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

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 antiox...

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Published inInternational journal of molecular sciences Vol. 24; no. 7; p. 6053
Main Authors Lin, Da-Wei, Hsu, Yung-Chien, Chang, Cheng-Chih, Hsieh, Ching-Chuan, Lin, Chun-Liang
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 23.03.2023
MDPI
Subjects
Antioxidants
Antioxidants - metabolism
Antioxidants - therapeutic use
B cells
Chronic kidney failure
Diabetes
Diabetic nephropathies
Diabetic Nephropathies - metabolism
Diabetic nephropathy
Endoplasmic reticulum
Genes
Genetic aspects
Genetic transcription
Homeostasis
Humans
Inflammation
Kelch-Like ECH-Associated Protein 1 - metabolism
Kidney - metabolism
Kidney diseases
Kinases
Medical research
Medicine, Experimental
Mitochondria
NF-E2-Related Factor 2 - metabolism
Oxidation
Oxidative Stress
Proteins
Reactive Oxygen Species - metabolism
Review
Transcription factors
Tumor necrosis factor-TNF
Type 2 diabetes
Ubiquitin
Taiwan
acute kidney injury (AKI)
diabetes nephropathy
reactive oxygen species (ROS)
reduction-oxidation (redox)
chronic kidney disease (CKD)
nuclear factor erythroid 2-related factor 2 (NRF2)
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms24076053

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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.
AbstractList 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.
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.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.
Audience Academic
Author Chang, Cheng-Chih
Lin, Da-Wei
Hsu, Yung-Chien
Lin, Chun-Liang
Hsieh, Ching-Chuan
AuthorAffiliation 3 Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 613, Taiwan
4 Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
6 Kidney Research Center, Chang Gung Memorial Hospital, Taipei 105, Taiwan
1 Department of Internal Medicine, St. Martin de Porres Hospital, Chiayi 600, Taiwan
7 Center for Shockwave Medicine and Tissue Engineering, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
2 Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
5 School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
AuthorAffiliation_xml – name: 2 Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
– name: 5 School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
– name: 4 Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
– name: 6 Kidney Research Center, Chang Gung Memorial Hospital, Taipei 105, Taiwan
– name: 1 Department of Internal Medicine, St. Martin de Porres Hospital, Chiayi 600, Taiwan
– name: 7 Center for Shockwave Medicine and Tissue Engineering, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
– name: 3 Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 613, Taiwan
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  surname: Lin
  fullname: Lin, Da-Wei
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  surname: Chang
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  surname: Hsieh
  fullname: Hsieh, Ching-Chuan
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  givenname: Chun-Liang
  orcidid: 0000-0002-5710-8405
  surname: Lin
  fullname: Lin, Chun-Liang
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37047024$$D View this record in MEDLINE/PubMed
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Issue 7
Keywords acute kidney injury (AKI)
diabetes nephropathy
reactive oxygen species (ROS)
reduction-oxidation (redox)
chronic kidney disease (CKD)
nuclear factor erythroid 2-related factor 2 (NRF2)
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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SecondaryResourceType review_article
Snippet Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all...
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SubjectTerms Antioxidants
Antioxidants - metabolism
Antioxidants - therapeutic use
B cells
Chronic kidney failure
Diabetes
Diabetic nephropathies
Diabetic Nephropathies - metabolism
Diabetic nephropathy
Endoplasmic reticulum
Genes
Genetic aspects
Genetic transcription
Homeostasis
Humans
Inflammation
Kelch-Like ECH-Associated Protein 1 - metabolism
Kidney - metabolism
Kidney diseases
Kinases
Medical research
Medicine, Experimental
Mitochondria
NF-E2-Related Factor 2 - metabolism
Oxidation
Oxidative Stress
Proteins
Reactive Oxygen Species - metabolism
Review
Transcription factors
Tumor necrosis factor-TNF
Type 2 diabetes
Ubiquitin
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Title Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases
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