ArticleEndocrinology2018
Nrf2 Deficiency Upregulates Intrarenal Angiotensin-Converting Enzyme-2 and Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy in Diabetic Mice.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 115 citations in OpenAlex.
- Renal tubule-specific Nrf2 deletion ameliorates diabetic kidney disease by attenuating glomerular hypertension and kidney injury in a mouse model of diabetes.Diabetologia · 2026Article
- Host-directed antiviral strategy targeting prohibitins: Mel56 suppresses influenza A virus and severe acute respiratory syndrome coronavirus 2 via modulation of antioxidant pathways and mitochondrial function.Microbiology spectrum · 2026Article
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Targeted activation of Nrf2 at sites of oxidative stress reverses doxorubicin-induced cognitive impairments in mice.Brain, behavior, and immunity · 2025Article
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses.Vaccines · 2025Article
- Suk-SaiYasna Remedy, a Traditional Thai Medicine, Mitigates Stress-Induced Cognitive Impairment via Keap1-Nrf2 Pathway.International journal of molecular sciences · 2025Article
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- The role and therapeutic potential of itaconate in lung disease.Cellular & molecular biology letters · 2024Review
- Edible mushroom (Anatomy & cell biology · 2024Article
- Interplay between the Redox System and Renal Tubular Transport.Antioxidants (Basel, Switzerland) · 2024Review
- Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Multiple Mechanisms of Action of SulfodyneAntioxidants (Basel, Switzerland) · 2024Article
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review.Journal of agricultural and food chemistry · 2024Review
- Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline.International journal of molecular sciences · 2024Review
- NRF2 in kidney physiology and disease.Physiological reports · 2024Review
- Effect of Diacetylcurcumin Manganese Complex on Rotenone-Induced Oxidative Stress, Mitochondria Dysfunction, and Inflammation in the SH-SY5Y Parkinson's Disease Cell Model.Molecules (Basel, Switzerland) · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined rat immortalized RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1-7) receptor (MasR) gene promoters. Genetic deletion of Nrf2 or pharmacological inhibition of Nrf2 in Akita mice attenuated hypertension, renal injury, tubulointerstitial fibrosis, and the urinary albumin/creatinine ratio. Furthermore, loss of Nrf2 upregulated RPTC Ace2 and MasR expression, increased urinary Ang 1-7 levels, and downregulated expression of Agt, ACE, and profibrotic genes in Akita mice. In cultured IRPTCs, Nrf2 small interfering RNA transfection or trigonelline treatment prevented high glucose stimulation of Nrf2 nuclear translocation, Agt, and ACE transcription with augmentation of Ace2 and MasR transcription, which was reversed by oltipraz. These data identify a mechanism, Nrf2-mediated stimulation of intrarenal RAS gene expression, by which chronic hyperglycemia induces hypertension and renal injury in diabetes.
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Registered trials
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