ArticlePloS one2013
Valproic acid treatment inhibits hypoxia-inducible factor 1α accumulation and protects against burn-induced gut barrier dysfunction in a rodent model.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Pooled it
- Enrichment of H3S28p and H3K9me2 Epigenetic Marks on Inflammatory-Associated Gene Promoters in Response to Severe Burn Injury.Life (Basel, Switzerland) · 2024Article
- Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.Critical care (London, England) · 2024Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- Histone deacetylase inhibitor attenuates intestinal mucosal injury in fatally scalded rats.Annals of translational medicine · 2022Article
- Maintenance of gut barrier integrity after injury: Trust your gut microRNAs.Journal of leukocyte biology · 2021Review
- Protective effects of PX478 on gut barrier in a mouse model of ethanol and burn injury.Journal of leukocyte biology · 2021Article
- Targeting the gut to prevent sepsis from a cutaneous burn.JCI insight · 2020Article
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Valproic acid inhibits the angiogenic potential of cervical cancer cells via HIF-1α/VEGF signals.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
- Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.Shock (Augusta, Ga.) · 2015Review
- microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1.European journal of medical research · 2015Article
- Alcohol Modulation of the Postburn Hepatic Response.Journal of burn care & research : official publication of the American Burn AssociationReview
- Remote Burn Injury Increases Pulmonary Histone Deacetylase 1 and Reduces Histone Acetylation.Journal of burn care & research : official publication of the American Burn AssociationArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveBurn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracellular barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression.
methodsRats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO2 cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1.
resultsBurn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1.
conclusionsThese results indicate that VPA can protect against burn-induced gut barrier dysfunction. These protective effects may be due to its inhibitory action on HIF-1α, leading to a reduction in intestinal VEGF and MLCK expression and minimizing ZO-1 degradation.
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Registered trials
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