Nrf2 Modulation in Oxidative Stress and Kidney Disease
Summary
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs the cellular antioxidant response and plays a pivotal role in maintaining redox homeostasis in renal tissues. Under basal conditions, Nrf2 is sequestered in the cytoplasm by its inhibitor Kelch-like ECH-associated protein 1 (Keap1) and targeted for proteasomal degradation. Oxidative stress, as encountered in acute kidney injury (AKI), diabetic kidney disease (DKD) and chronic kidney disease (CKD), induces conformational changes in Keap1 or additional regulatory kinases, permitting Nrf2 nuclear translocation. In the nucleus, Nrf2 binds antioxidant response elements (AREs) to drive expression of cytoprotective genes coding for enzymes such as heme oxygenase-1, NAD(P)H quinone oxidoreductase 1 and glutathione biosynthetic machinery. Dysregulation of this axis contributes to mitochondrial dysfunction, lipid peroxidation, inflammasome activation and fibrotic remodelling in glomerular and tubular compartments. Preclinical models demonstrate that genetic or pharmacological manipulation of Nrf2 can mitigate oxidative injury, suppress pro-inflammatory cascades and attenuate progression from AKI to CKD. Yet the clinical translation of potent Nrf2 agonists has been tempered by off-target effects, underscoring the need for safer modulators and deeper insight into context-specific regulation.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Nrf2 Modulation in Oxidative Stress and Kidney Disease publication trend
The graph below shows the total number of articles in nrf2 modulation in oxidative stress and kidney disease across all publications each year (not limited to Nature Index journals).
Technical terms
Nrf2: A transcription factor that activates genes encoding antioxidant and detoxification enzymes in response to oxidative stress.
Keap1: A cytoplasmic protein that binds Nrf2 under resting conditions and promotes its ubiquitin-mediated degradation.
Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can damage DNA, proteins and lipids when accumulated.
Antioxidant response element (ARE): A cis-acting DNA sequence in gene promoters recognised by Nrf2 to initiate transcription of cytoprotective genes.
NLRP3 inflammasome: A multiprotein complex that senses cellular stress and drives interleukin‐1β maturation, contributing to sterile inflammation in kidney injury.
References
- NRF2 Deficiency Attenuates Diabetic Kidney Disease in Db/Db Mice via Down-Regulation of Angiotensinogen, SGLT2, CD36, and FABP4 Expression and Lipid Accumulation in Renal Proximal Tubular Cells. Antioxidants (2023).
- Activation of the Nrf2/ARE signaling pathway ameliorates hyperlipidemia-induced renal tubular epithelial cell injury by inhibiting mtROS-mediated NLRP3 inflammasome activation. Frontiers in Immunology (2024).
- Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives. Biomolecules (2022).
- GSK3β-mediated Keap1-independent regulation of Nrf2 antioxidant response: A molecular rheostat of acute kidney injury to chronic kidney disease transition. Redox Biology (2019).
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.