ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2014
Keap1 inhibition attenuates glomerulosclerosis.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
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- Effects of grape seed-derived proanthocyanidin B2 pretreatment on oxidative stress, endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells in renal ischemia-reperfusion injury model of mice.International urology and nephrology · 2023Article
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- Nrf2 Protein Serum Concentration in Human CKD Shows a Biphasic Behavior.Antioxidants (Basel, Switzerland) · 2023Article
- Proximal tubule cells in blood and urine as potential biomarkers for kidney disease biopsy.PeerJ · 2023Article
- Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Indirect podocyte injury manifested in a partial podocytectomy mouse model.American journal of physiology. Renal physiology · 2021Article
- Eat Your Broccoli: Oxidative Stress, NRF2, and Sulforaphane in Chronic Kidney Disease.Nutrients · 2021Review
- Treatment of Diabetic Kidney Disease: Current and Future.Diabetes & metabolism journal · 2021Review
- Protective Role of Nrf2 in Renal Disease.Antioxidants (Basel, Switzerland) · 2020Review
- Patent Review (2017-2020) of the Keap1/Nrf2 Pathway Using PatSeer Pro: Focus on Autoimmune Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Emerging drugs for treatment of focal segmental glomerulosclerosis.Expert opinion on emerging drugs · 2020Review
- Roles of Nrf2 in Protecting the Kidney from Oxidative Damage.International journal of molecular sciences · 2020Review
- Article
- In vivo and in vitro knockout system labelled using fluorescent protein via microhomology-mediated end joining.Life science alliance · 2020Article
- Intrarenal Transplantation of Hypoxic Preconditioned Mesenchymal Stem Cells Improves Glomerulonephritis through Anti-Oxidation, Anti-ER Stress, Anti-Inflammation, Anti-Apoptosis, and Anti-Autophagy.Antioxidants (Basel, Switzerland) · 2019Article
- GSK3β-mediated Keap1-independent regulation of Nrf2 antioxidant response: A molecular rheostat of acute kidney injury to chronic kidney disease transition.Redox biology · 2019Article
- Forced expression of vascular endothelial growth factor-A in podocytes decreases mesangial cell numbers and attenuates endothelial cell differentiation in the mouse glomerulus.Clinical and experimental nephrology · 2018Article
- Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages.Frontiers in pharmacology · 2018Review
- Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress.The Journal of biological chemistry · 2017Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundNFE2-related factor 2 (Nrf2) is a master regulatory transcription factor for antioxidant genes. Inhibition of its adaptor protein, Kelch-like ECH-associated protein 1 (Keap1), activates Nrf2. Podocyte injury triggers the progressive deterioration of glomerular damage toward glomerulosclerosis. We examined whether modulation of the Keap1-Nrf2 system has an impact on this process.
methodsNrf2 null-mutant (KO) and Keap1 hypomorphic knockdown (KD) mice were crossed with NEP25 mice, in which podocyte-specific injury can be induced by an immunotoxin.
resultsThiobarbituric acid reactive substances, 8-hydroxydeoxyguanosine and phosphorylated JNK were increased in the injured NEP25 kidney. Real-time PCR revealed that Keap1 KD upregulated Nrf2 target genes, including Gclc, Gclm, Gstp1, Gstp2 and Nqo1 in the glomerulus. However, podocyte injury did not upregulate these genes in Keap1 wild-type mice, nor did it further increase the expression of those genes in Keap1 KD mice. Three weeks after the induction of podocyte injury, glomerulosclerosis was considerably more attenuated in Keap1 KD mice than in control mice (median sclerosis index, 0.27 versus 3.03, on a 0-4 scale). Keap1 KD mice also showed considerably preserved nephrin staining (median index, 6.76 versus 0.91, on a 0-8 scale) and decreased glomeruli containing desmin-positive injured podocytes (median percentage, 24.5% versus 85.8%), along with a decrease in mRNAs for Fn1, Tgfb1, Col4a4 and Col1a2.
conclusionsThus, podocyte injury cannot effectively activate Nrf2, but Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases.
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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.