The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases
Over 10% of the global population is at risk to kidney disorders. Nuclear factor erythroid-derived 2-related factor 2 (NRF2), a pivotal regulator of redox homeostasis, orchestrates antioxidant response that effectively counters oxidative stress and inflammatory response in a variety of acute pathoph...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004543 |
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| author | Yiying Bian Jize Dong Zhengsheng Zhou Hua Zhou Yuanyuan Xu Qiang Zhang Chengjie Chen Jingbo Pi |
| author_facet | Yiying Bian Jize Dong Zhengsheng Zhou Hua Zhou Yuanyuan Xu Qiang Zhang Chengjie Chen Jingbo Pi |
| author_sort | Yiying Bian |
| collection | DOAJ |
| description | Over 10% of the global population is at risk to kidney disorders. Nuclear factor erythroid-derived 2-related factor 2 (NRF2), a pivotal regulator of redox homeostasis, orchestrates antioxidant response that effectively counters oxidative stress and inflammatory response in a variety of acute pathophysiological conditions, including acute kidney injury (AKI) and early stage of renal toxicity. However, if persistently activated, NRF2-induced transcriptional cascade may disrupt normal cell signaling and contribute to numerous chronic pathogenic processes such as fibrosis. In this concise review, we assembled experimental evidence to reveal the cell- and pathophysiological condition-specific roles of NRF2 in renal chemical toxicity, AKI, and chronic kidney disease (CKD), all of which are closely associated with oxidative stress and inflammation. By incorporating pertinent research findings on NRF2 activators, we dissected the spatiotemporal roles of NRF2 in distinct nephrotoxic settings and kidney diseases. Herein, NRF2 exhibits diverse expression patterns and downstream gene profiles across distinct kidney regions and cell types, and during specific phases of nephropathic progression. These changes are directly or indirectly connected to altered antioxidant defense, damage repair, inflammatory response, regulated cell death and fibrogenesis, culminating ultimately in either protective or deleterious outcomes. The spatiotemporal and paradoxical characteristics of NRF2 in mitigating nephrotoxicity suggest that translational application of NRF2 activation strategy for prevention and interventions of kidney injury are unlikely to be straightforward – right timing and spatial precision must be taken into consideration. |
| format | Article |
| id | doaj-art-e14d49a809b04de295e03166a515aa19 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-e14d49a809b04de295e03166a515aa192025-01-14T04:12:12ZengElsevierRedox Biology2213-23172025-02-0179103476The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseasesYiying Bian0Jize Dong1Zhengsheng Zhou2Hua Zhou3Yuanyuan Xu4Qiang Zhang5Chengjie Chen6Jingbo Pi7Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China; Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic (China Medical University), China; Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, ChinaDepartment of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China; Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic (China Medical University), China; Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, ChinaDepartment of Nephrology, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China; Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic (China Medical University), China; Group of Chronic Disease and Environmental Genomics, School of Public Health, China Medical University, ChinaGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, GA, 30322, USAKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China; Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic (China Medical University), China; Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China; Corresponding author. Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China.Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China; Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic (China Medical University), China; Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China; Corresponding author. Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention, Ministry of Education (China Medical University), China.Over 10% of the global population is at risk to kidney disorders. Nuclear factor erythroid-derived 2-related factor 2 (NRF2), a pivotal regulator of redox homeostasis, orchestrates antioxidant response that effectively counters oxidative stress and inflammatory response in a variety of acute pathophysiological conditions, including acute kidney injury (AKI) and early stage of renal toxicity. However, if persistently activated, NRF2-induced transcriptional cascade may disrupt normal cell signaling and contribute to numerous chronic pathogenic processes such as fibrosis. In this concise review, we assembled experimental evidence to reveal the cell- and pathophysiological condition-specific roles of NRF2 in renal chemical toxicity, AKI, and chronic kidney disease (CKD), all of which are closely associated with oxidative stress and inflammation. By incorporating pertinent research findings on NRF2 activators, we dissected the spatiotemporal roles of NRF2 in distinct nephrotoxic settings and kidney diseases. Herein, NRF2 exhibits diverse expression patterns and downstream gene profiles across distinct kidney regions and cell types, and during specific phases of nephropathic progression. These changes are directly or indirectly connected to altered antioxidant defense, damage repair, inflammatory response, regulated cell death and fibrogenesis, culminating ultimately in either protective or deleterious outcomes. The spatiotemporal and paradoxical characteristics of NRF2 in mitigating nephrotoxicity suggest that translational application of NRF2 activation strategy for prevention and interventions of kidney injury are unlikely to be straightforward – right timing and spatial precision must be taken into consideration.http://www.sciencedirect.com/science/article/pii/S2213231724004543NRF2Oxidative stressRenal toxicityKidney diseases |
| spellingShingle | Yiying Bian Jize Dong Zhengsheng Zhou Hua Zhou Yuanyuan Xu Qiang Zhang Chengjie Chen Jingbo Pi The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases Redox Biology NRF2 Oxidative stress Renal toxicity Kidney diseases |
| title | The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases |
| title_full | The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases |
| title_fullStr | The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases |
| title_full_unstemmed | The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases |
| title_short | The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases |
| title_sort | spatiotemporal and paradoxical roles of nrf2 in renal toxicity and kidney diseases |
| topic | NRF2 Oxidative stress Renal toxicity Kidney diseases |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004543 |
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