ArticleThe Journal of clinical investigation2016
Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
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Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Lipid homeostasis in diabetic kidney disease.International journal of biological sciences · 2024Pooled it
- Intrinsic tumor necrosis factor-α pathway is activated in a subset of patients with focal segmental glomerulosclerosis.PloS one · 2019Trial
- Treatment outcomes and ongoing pediatric trials in steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Review
- Modulation of the Apolipoprotein M/S1PR4 Pathway Reduces Podocyte Lipid Overload in Alport Syndrome via Distinct Autophagy and Efflux Mechanisms.Journal of the American Society of Nephrology : JASN · 2026Article
- Molecular mechanisms and novel therapeutic targets of diabetic kidney disease.Chinese medical journal · 2026Review
- Lipid metabolic dysregulation in diabetic kidney disease: mechanisms, cellular impact, and therapeutic strategies.Journal of clinical & translational endocrinology · 2026Review
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- From RAAS blockade to regenerative medicine: evolving treatment strategies in Alport syndrome.Pediatric nephrology (Berlin, Germany) · 2026Review
- Hyperlipidemia in membranous nephropathy.Clinical kidney journal · 2026Review
- Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026Review
- SIRT6 Attenuates Angiotensin II-Induced Podocyte Cholesterol Accumulation and Injury via Negative Modulation of SREBP2.Kidney & blood pressure research · 2026Article
- The lipid-podocyte axis: emerging clues in membranous nephropathy pathogenesis.Frontiers in medicine · 2026Review
- Hypoxia-inducible factor 2α overexpression in podocytes ameliorates lipid metabolism disorders in diabetic kidney disease by inhibiting S1P.Renal failure · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.Journal of advanced research · 2025Article
- Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications.Current issues in molecular biology · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Novel Lipophagy Inducers as Potential Therapeutics for Lipid Metabolism Disorders.ACS chemical biology · 2025Article
- Kidney lipid metabolism: impact on pediatric kidney diseases and modulation by early-life nutrition.Pediatric nephrology (Berlin, Germany) · 2025Review
- Podocyte-related biomarkers' role in evaluating renal toxic effects of silver nanoparticles with the possible ameliorative role of resveratrol in adult male albino rats.Toxicology reports · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 4 countries.
Funding
Abstract
High levels of circulating TNF and its receptors, TNFR1 and TNFR2, predict the progression of diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated the function of local and systemic TNF in podocyte injury. We cultured human podocytes with sera collected from DKD patients, who displayed elevated TNF levels, and focal segmental glomerulosclerosis (FSGS) patients, whose TNF levels resembled those of healthy patients. Exogenous TNF administration or local TNF expression was equally sufficient to cause free cholesterol-dependent apoptosis in podocytes by acting through a dual mechanism that required a reduction in ATP-binding cassette transporter A1-mediated (ABCA1-mediated) cholesterol efflux and reduced cholesterol esterification by sterol-O-acyltransferase 1 (SOAT1). TNF-induced albuminuria was aggravated in mice with podocyte-specific ABCA1 deficiency and was partially prevented by cholesterol depletion with cyclodextrin. TNF-stimulated free cholesterol-dependent apoptosis in podocytes was mediated by nuclear factor of activated T cells 1 (NFATc1). ABCA1 overexpression or cholesterol depletion was sufficient to reduce albuminuria in mice with podocyte-specific NFATc1 activation. Our data implicate an NFATc1/ABCA1-dependent mechanism in which local TNF is sufficient to cause free cholesterol-dependent podocyte injury irrespective of TNF, TNFR1, or TNFR2 serum levels.
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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.