ArticleDiabetes2013
Mammalian target of rapamycin regulates Nox4-mediated podocyte depletion in diabetic renal injury.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review.BMC nephrology · 2019Pooled it
- Cell-state- and compartment-dependent PI3K/Akt redox signaling in chronic kidney disease: mechanisms and translational implications.Frontiers in pharmacology · 2026Review
- Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction.Physiological research · 2025Review
- Genetic and Pharmacological Inhibition of NOX4 Protects Against Rhabdomyolysis-Induced Acute Kidney Injury Through Suppression of Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Jinlida granules alleviate podocyte apoptosis and mitochondrial dysfunction via the AMPK/PGC‑1α pathway in diabetic nephropathy.International journal of molecular medicine · 2025Article
- High glucose couples DJ-1 with PTEN to activate PDGFRβ for renal proximal tubular cell injury.PloS one · 2025Article
- Nox4-SH3YL1 complex is involved in diabetic nephropathy.iScience · 2024Article
- COL4A3 Mutation Induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2.Kidney international reports · 2023Article
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Rapamycin Inhibits Osteoclastogenesis and Prevents LPS-Induced Alveolar Bone Loss by Oxidative Stress Suppression.ACS omega · 2023Article
- Unraveling the Crosstalk between Lipids and NADPH Oxidases in Diabetic Kidney Disease.Pharmaceutics · 2023Review
- Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades.Cellular and molecular life sciences : CMLS · 2022Article
- Modes of podocyte death in diabetic kidney disease: an update.Journal of nephrology · 2022Review
- Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases.Biomedicines · 2021Article
- CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity.International journal of molecular sciences · 2021Article
- Article
- COVID-19 and diabetes mellitus: how one pandemic worsens the other.Reviews in endocrine & metabolic disorders · 2020Review
- TGFβ acts through PDGFRβ to activate mTORC1 via the Akt/PRAS40 axis and causes glomerular mesangial cell hypertrophy and matrix protein expression.The Journal of biological chemistry · 2020Article
- NOX4/HHypertension (Dallas, Tex. : 1979) · 2020Article
- Glucose 6-Phosphate Accumulates via Phosphoglucose Isomerase Inhibition in Heart Muscle.Circulation research · 2020Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Pharmacological doses of the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduce albuminuria in diabetes. We explored the hypothesis that mTOR mediates podocyte injury in diabetes. High glucose (HG) induces apoptosis of podocytes, inhibits AMP-activated protein kinase (AMPK) activation, inactivates tuberin, and activates mTOR. HG also increases the levels of Nox4 and Nox1 and NADPH oxidase activity. Inhibition of mTOR by low-dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase activity, and podocyte apoptosis. Inhibition of mTOR had no effect on AMPK or tuberin phosphorylation, indicating that mTOR is downstream of these signaling molecules. In isolated glomeruli of OVE26 mice, there is a similar decrease in the activation of AMPK and tuberin and activation of mTOR with increase in Nox4 and NADPH oxidase activity. Inhibition of mTOR by a small dose of rapamycin reduces podocyte apoptosis and attenuates glomerular injury and albuminuria. Our data provide evidence for a novel function of mTOR in Nox4-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. Thus, mTOR and/or NADPH oxidase inhibition may represent a therapeutic modality of diabetic kidney disease.
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