ArticleAntioxidants (Basel, Switzerland)2022
Suppression of NRF2 Activity by HIF-1α Promotes Fibrosis after Ischemic Acute Kidney Injury.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- The mechanism and therapeutic prospect of HIF-1 α/BNIP3 pathway in regulating mitophagy in tubulointerstitial fibrosis.Renal failure · 2026Review
- VHL-recruiting PROTAC attenuates AKI-CKD transition via simultaneous degradation of Smad3 and stabilization of HIF-2α.Cell death & disease · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- SLC25A11-mediated reprogramming of mitochondrial redox state and lipid peroxidation confers NRF2-dependent ferroptosis resistance in biliary tract cancer.Cellular & molecular biology letters · 2026Article
- Low hypoxia tolerance as a determinant of the proinflammatory phenotype: a trained immunity perspective.Frontiers in immunology · 2026Review
- Mechanistic elucidation of Wuling Powder targeting macrophage polarization to ameliorate renal ischemia-reperfusion injury via multidimensional computational systems pharmacology coupled with experimental validation.Frontiers in pharmacology · 2026Article
- From Electron Imbalance to Network Collapse: Decoding the Redox Code of Ischemic Stroke for Biomarker-Guided Precision Neuroprotection.International journal of molecular sciences · 2025Review
- Expression characteristics of dual-specificity phosphatase 2 and hypoxia-inducible factor-1α in acute kidney injury and preliminary study of the effect of dual-specificity phosphatase 2 on HK-2 cells.Experimental physiology · 2025Article
- Network expression analysis identifies and experimentally validates the involvement of Fosb in acute kidney injury.FASEB bioAdvances · 2025Article
- Oxidative stress and NRF2 signaling in kidney injury.Toxicological research · 2025Review
- The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets.Molecular and cellular biochemistry · 2025Review
- Mechanisms and therapeutic prospects of hypoxia-inducible factor 1-alpha in acute kidney injury: a systematic review.Frontiers in cell and developmental biology · 2025Review
- Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.Current drug targets · 2025Review
- Beneficial effects of food-medicine homologous herbs for patients with diabetic kidney disease.Frontiers in immunology · 2025Review
- Oral Carnosine Supplementation Preserves Vascular Function of Sprague Dawley Rats on a High-Salt Diet via Restored Antioxidative Defence.Nutrients · 2024Article
- Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.Experimental & molecular medicine · 2024Review
- NRF2 in kidney physiology and disease.Physiological reports · 2024Review
- Targeting NRF2 to promote epithelial repair.Biochemical Society transactions · 2023Review
- β-Cryptoxanthin Maintains Mitochondrial Function by Promoting NRF2 Nuclear Translocation to Inhibit Oxidative Stress-Induced Senescence in HK-2 Cells.International journal of molecular sciences · 2023Article
- Myrrh Essential Oil Mitigates Renal Ischemia/Reperfusion-Induced Injury.Current issues in molecular biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acute kidney injury (AKI) is a rapid decline in renal function and can occur after ischemia/reperfusion injury (IRI) to the tubular epithelia. The nuclear factor erythroid-2-related factor 2 (NRF2) pathway protects against AKI and AKI-to-chronic kidney disease (CKD) progression, but we previously demonstrated that severe IRI maladaptively reduced NRF2 activity in mice. To understand the mechanism of this response, we subjected C57BL/6J mice to unilateral kidney IRI with ischemia times that were titrated to induce mild to severe injury. Mild IRI increased NRF2 activity and was associated with renal recovery, whereas severe IRI decreased NRF2 activity and led to progressive CKD. Due to these effects of ischemia, we tested the hypothesis that hypoxia-inducible factor-1α (HIF-1α) mediates NRF2 activity. To mimic mild and severe ischemia, we activated HIF-1α in HK-2 cells in nutrient-replete or nutrient-deficient conditions. HIF-1α activation in nutrient-replete conditions enhanced NRF2 nuclear localization and activity. However, in nutrient-deficient conditions, HIF-1α activation suppressed NRF2 nuclear localization and activity. Nuclear localization was rescued with HIF-1α siRNA knockdown. Our results suggest that severe ischemic AKI leads to HIF-1α-mediated suppression of NRF2, leading to AKI-to-CKD progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.