ArticleThe Journal of pharmacology and experimental therapeutics2016
Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 83 citations in OpenAlex.
- Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.Biomedicines · 2026Review
- Prenatal supplementation with the gut-derived tryptophan metabolite indole-3-propionic acid alleviates colitis susceptibility in maternal immune-activated offspring mice.Journal of advanced research · 2026Article
- Lipid-derived microbial metabolites at the gut-liver interface: regulation of intestinal barrier function, immune signaling, and metabolic inflammation.Frontiers in physiology · 2026Review
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- Exploring the Therapeutic Role of Pregnane X Receptor Activation in Acute Kidney Injury: Mechanisms and Clinical Implications.Current molecular medicine · 2026Review
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- The gut-microbiota-brain axis: Focus on gut steroids.Journal of neuroendocrinology · 2025Review
- Bile acids and their receptors in hepatic immunity.Liver research (Beijing, China) · 2025Review
- The gut microbiota and its metabolites: novel therapeutic targets for inflammatory bowel disease.Frontiers in immunology · 2025Review
- Indole-3-propionic acid enhances growth performance and reduces diarrhea via modulating redox status and intestinal inflammation in weaned piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Gut microbial metabolism in Alzheimer's disease and related dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Bacteria and Allergic Diseases.International journal of molecular sciences · 2024Review
- Nuclear Receptors and Stress Response Pathways Associated with the Development of Oral Mucositis Induced by Antineoplastic Agents.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease.Intestinal research · 2024Review
- Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death.Journal of cellular and molecular medicine · 2023Article
- IPA and its precursors differently modulate the proliferation, differentiation, and integrity of intestinal epithelial cells.Nutrition research and practice · 2023Article
- Terpenes: Modulating anti-inflammatory signaling in inflammatory bowel disease.Pharmacology & therapeutics · 2023Review
- Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases.Biomedicines · 2022Review
- Role of Bile Acids and Nuclear Receptors in Acupuncture in Improving Crohn's Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Dual therapy with zinc acetate and rifaximin prevents from ethanol-induced liver fibrosis by maintaining intestinal barrier integrity.World journal of gastroenterology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR [rifaximin and [[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethenylidene]bis-phosphonic acid tetraethyl ester (SR12813); 10 μM] protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR [pregnenolone 16α-carbonitrile (PCN)] attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr-/-, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.
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.