ArticleAmerican journal of physiology. Renal physiology2011
TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
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- Direct ionic stress sensing and mitigation by the transcription factor NFAT5.Science advances · 2025Article
- Hyperosmolar stress induces monocyte chemoattractant protein 1 expression in retinal pigmented epithelial arising retinal pigmented epithelial 19 cells.Molecular vision · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Direct ionic stress sensing and mitigation by the transcription factor NFAT5.bioRxiv : the preprint server for biology · 2023Article
- Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis.eLife · 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 old and the new about the contractile vacuole of Trypanosoma cruzi.The Journal of eukaryotic microbiology · 2022Review
- Review
- The C. elegans Hypertonic Stress Response: Big Insights from Shrinking Worms.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.International journal of molecular sciences · 2021Review
- Farnesoid X receptor: a potential therapeutic target in multiple organs.Histology and histopathology · 2020Review
- EnterotoxigenicGut microbes · 2020Article
- The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress.PLoS genetics · 2020Article
- Article
- Single-Cell RNA Sequencing Reveals Renal Endothelium Heterogeneity and Metabolic Adaptation to Water Deprivation.Journal of the American Society of Nephrology : JASN · 2020Article
- TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging.Nature communications · 2019Article
- NFAT5 up-regulates expression of the kidney-specific ubiquitin ligase geneThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that the genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Of over 100 potentially new TonEBP-regulated genes, we selected seven for further analyses and found that their expressions were all dependent on TonEBP. RNA interference experiments showed that some of these genes, asporin, insulin-like growth factor-binding protein-5 and -7, and an extracellular lysophospholipase D, plus heat shock protein 70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
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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.