ArticlePloS one2014
4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- Pharmacological inhibition of endoplasmic reticulum stress ameliorates polystyrene nanoplastic-induced renal injury in female Wistar rats.Journal of molecular histology · 2026Article
- Caveolin-1 Stabilizes SERCA2 to Counteract Acute Kidney Injury via Suppression of CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNF126 mediates fetal growth restriction via ubiquitination-dependent degradation of the MYH9/MYH10 complex.iScience · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- The Influence of Sex and Hormones on Organelle Stress in Kidney Injury: Insights from Preclinical Models.Biology · 2026Review
- Organ-specific apoptotic pathways induced by micro- and nanoplastics: a systematic review ofFrontiers in toxicology · 2026Review
- Oxidative stress and endoplasmic reticulum stress in acute kidney injury: mechanistic crosstalk and therapeutic modulation.Frontiers in medicine · 2026Review
- Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease.Nature reviews. Nephrology · 2025Review
- Sephin1 suppresses ER stress-induced cell death by inhibiting the formation of PP2A holoenzyme.Cell death & disease · 2025Article
- Article
- TunR2, a novel mode-of-action tunicamycin-type antibiotic: Pharmacokinetics in C57BL/6 mouse and Holstein cattle.PloS one · 2025Article
- Evaluation of the cytotoxicity and antibacterial activity of a synthetic tunicamycin derivative againstFrontiers in microbiology · 2025Article
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- Exploration of the renoprotective effect of Yi-Shen-Hua-Shi granules on db/db mice and the mechanism of podocyte apoptosis based on the GRP78/CHOP signaling pathway.Frontiers in pharmacology · 2025Article
- Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4.Biomedicines · 2024Article
- Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.Biomolecules · 2024Review
- 4-Phenylbutyric Acid Treatment Reduces Low-Molecular-Weight Proteinuria in aInternational journal of molecular sciences · 2024Article
- Article
- Targeting Endoplasmic Reticulum for Novel Therapeutics and Monitoring in Acute Kidney Injury.Nephron · 2023Review
- Emerging links between endoplasmic reticulum stress responses and acute kidney injury.American journal of physiology. Cell physiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Different forms of acute kidney injury (AKI) have been associated with endoplasmic reticulum (ER) stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA) is an FDA approved substance used in children who suffer from urea cycle disorders. 4-PBA acts as an ER stress inhibitor by aiding in protein folding at the molecular level and preventing misfolded protein aggregation. The main objective of this study was to determine if 4-PBA could protect from AKI induced by ER stress, as typified by the TM-model, and what mechanism(s) of 4-PBA's action were responsible for protection. C57BL/6 mice were treated with saline, TM or TM plus 4-PBA. 4-PBA partially protected the anatomic segment most susceptible to damage, the outer medullary stripe, from TM-induced AKI. In vitro work showed that 4-PBA protected human proximal tubular cells from apoptosis and TM-induced CHOP expression, an ER stress inducible proapoptotic gene. Further, immunofluorescent staining in the animal model found similar protection by 4-PBA from CHOP nuclear translocation in the tubular epithelium of the medulla. This was accompanied by a reduction in apoptosis and GRP78 expression. CHOP(-/-) mice were protected from TM-induced AKI. The protective effects of 4-PBA extended to the ultrastructural integrity of proximal tubule cells in the outer medulla. When taken together, these results indicate that 4-PBA acts as an ER stress inhibitor, to partially protect the kidney from TM-induced AKI through the repression of ER stress-induced CHOP expression.
Indexed as
Identifiers
What OpenQuestion holds
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.