ArticleMolecular and cellular biology2013
Sestrin 2 and AMPK connect hyperglycemia to Nox4-dependent endothelial nitric oxide synthase uncoupling and matrix protein expression.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 135 citations in OpenAlex.
- Microvesicle-Derived Redox Signatures as Mediators of Endothelial Dysfunction in Diabetes.International journal of molecular sciences · 2026Article
- Interplay Between Sestrin Proteins and Ferroptosis: A Comprehensive Review of Regulatory Mechanisms.Molecular biotechnology · 2026Review
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- Sestrins: a new therapeutic target for endothelial dysfunction and cardiovascular disease prevention.Annals of medicine · 2025Review
- p53-regulated SESN1 and SESN2 regulate cell proliferation and cell death through control of STAT3.Cell communication and signaling : CCS · 2025Article
- The Emerging Role of Long Noncoding RNAs in Sorafenib Resistance Within Hepatocellular Carcinoma.Cancers · 2024Review
- Review
- Exogenous Nucleotides Ameliorate Insulin Resistance Induced by Palmitic Acid in HepG2 Cells through the IRS-1/AKT/FOXO1 Pathways.Nutrients · 2024Article
- Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia.The Journal of clinical endocrinology and metabolism · 2023Article
- Crabtree effect in kidney proximal tubule cells via late-stage glycolytic intermediates.iScience · 2023Article
- SGLT2 Inhibitor-Dapagliflozin Attenuates Diabetes-Induced Renal Injury by Regulating Inflammation through a CYP4A/20-HETE Signaling Mechanism.Pharmaceutics · 2023Article
- Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023Review
- Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy.Journal of diabetes research · 2023Review
- Autophagy and its therapeutic potential in diabetic nephropathy.Frontiers in endocrinology · 2023Review
- Sestrin2 attenuates renal damage by regulating Hippo pathway in diabetic nephropathy.Cell and tissue research · 2022Article
- Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades.Cellular and molecular life sciences : CMLS · 2022Article
- Sestrin2 remedies podocyte injury via orchestrating TSP-1/TGF-β1/Smad3 axis in diabetic kidney disease.Cell death & disease · 2022Article
- Inhibition of ChREBP ubiquitination via the ROS/Akt-dependent downregulation of Smurf2 contributes to lysophosphatidic acid-induced fibrosis in renal mesangial cells.Journal of biomedical science · 2022Article
- Renal mitochondrial injury in the pathogenesis of CKD: mtDNA and mitomiRs.Clinical science (London, England : 1979) · 2022Review
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mesangial matrix accumulation is an early feature of glomerular pathology in diabetes. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. Here, we demonstrate that, in glomerular mesangial cells (MCs), endothelial nitric oxide synthase (eNOS) is uncoupled upon exposure to high glucose (HG), with enhanced generation of reactive oxygen species (ROS) and decreased production of nitric oxide. Peroxynitrite mediates the effects of HG on eNOS dysfunction. HG upregulates Nox4 protein, and inhibition of Nox4 abrogates the increase in ROS and peroxynitrite generation, as well as the eNOS uncoupling triggered by HG, demonstrating that Nox4 functions upstream from eNOS. Importantly, this pathway contributes to HG-induced MC fibronectin accumulation. Nox4-mediated eNOS dysfunction was confirmed in glomeruli of a rat model of type 1 diabetes. Sestrin 2-dependent AMP-activated protein kinase (AMPK) activation attenuates HG-induced MC fibronectin synthesis through blockade of Nox4-dependent ROS and peroxynitrite generation, with subsequent eNOS uncoupling. We also find that HG negatively regulates sestrin 2 and AMPK, thereby promoting Nox4-mediated eNOS dysfunction and increased fibronectin. These data identify a protective function for sestrin 2/AMPK and potential targets for intervention to prevent fibrotic injury in diabetes.
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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.