ArticleMolecular biology of the cell2010
Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB activity.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- The Role of NF-κB in Peritoneal Fibrosis and Adhesion in Humans and Animals: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- A novel high-throughput single-molecule technique DNA curtain: Applications for DNA metabolism.Molecules and cells · 2025Review
- Hyperosmolar stress induces monocyte chemoattractant protein 1 expression in retinal pigmented epithelial arising retinal pigmented epithelial 19 cells.Molecular vision · 2025Article
- Article
- The NF-κB/FXR/TonEBP pathway protects renal medullary interstitial cells against hypertonic stress.Journal of cellular and molecular medicine · 2024Article
- TonEBP: A Key Transcription Factor in Microglia Following Intracerebral Hemorrhage Induced-Neuroinflammation.International journal of molecular sciences · 2024Article
- Sterile inflammation of peritoneal membrane caused by peritoneal dialysis: focus on the communication between immune cells and peritoneal stroma.Frontiers in immunology · 2024Review
- High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells.International journal of molecular sciences · 2023Article
- Alternations of NF-κB Signaling by Natural Compounds in Muscle-Derived Cancers.International journal of molecular sciences · 2023Review
- Modulation of mucin secretion using combined polyethylene glycol-propylene glycol topical formulation in a hyperosmotic stress-based explant model.Indian journal of ophthalmology · 2023Article
- Change in Metabolomic Profile Associated with an Average Increase in Plain Water Intake of >+ 1 L/Day, Sustained Over 4 Weeks, in Healthy Young Men with Initial Total Water Intake Below 2 L/Day.Paracelsus proceedings of experimental medicine · 2023Article
- The Role of Nuclear Factor of Activated T Cells 5 in Hyperosmotic Stress-Exposed Human Lens Epithelial Cells.International journal of molecular sciences · 2021Article
- NFAT5 Amplifies Antipathogen Responses by Enhancing Chromatin Accessibility, H3K27 Demethylation, and Transcription Factor Recruitment.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.International journal of molecular sciences · 2021Review
- Description of a Novel Mechanism Possibly Explaining the Antiproliferative Properties of Glucocorticoids in Duchenne Muscular Dystrophy Fibroblasts Based on Glucocorticoid Receptor GR and NFAT5.International journal of molecular sciences · 2020Article
- The evolving role of TonEBP as an immunometabolic stress protein.Nature reviews. Nephrology · 2020Review
- Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation.JCI insight · 2020Article
- Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling.International journal of molecular sciences · 2019Article
- Amelioration of Lipopolysaccharide-Induced Nephrotic Proteinuria by NFAT5 Depletion Involves Suppressed NF-κB Activity.Inflammation · 2019Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Tonicity-responsive binding-protein (TonEBP or NFAT5) is a widely expressed transcription factor whose activity is regulated by extracellular tonicity. TonEBP plays a key role in osmoprotection by binding to osmotic response element/TonE elements of genes that counteract the deleterious effects of cell shrinkage. Here, we show that in addition to this "classical" stimulation, TonEBP protects cells against hypertonicity by enhancing nuclear factor-κB (NF-κB) activity. We show that hypertonicity enhances NF-κB stimulation by lipopolysaccharide but not tumor necrosis factor-α, and we demonstrate overlapping protein kinase B (Akt)-dependent signal transduction pathways elicited by hypertonicity and transforming growth factor-α. Activation of p38 kinase by hypertonicity and downstream activation of Akt play key roles in TonEBP activity, IκBα degradation, and p65 nuclear translocation. TonEBP affects neither of these latter events and is itself insensitive to NF-κB signaling. Rather, we reveal a tonicity-dependent interaction between TonEBP and p65 and show that NF-κB activity is considerably enhanced after binding of NF-κB-TonEBP complexes to κB elements of NF-κB-responsive genes. We demonstrate the key roles of TonEBP and Akt in renal collecting duct epithelial cells and in macrophages. These findings reveal a novel role for TonEBP and Akt in NF-κB activation on the onset of hypertonic challenge.
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Registered trials
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.