ArticleExperimental & molecular medicine2021
LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways.
Article in Experimental & molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
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- RELA Ablation Contributes to Progression of Hepatocellular Carcinoma with TP53Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Constitutive Androstane Receptor in Macrophages Regulates Toll-Like Receptor 4-Mediated Innate Immune Responses Against Endotoxemic Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Restraint Stress Disrupted Intestinal Homeostasis via 5-HT/HTR7/Wnt/β-Catenin/NF-kB Signaling.International journal of molecular sciences · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Formoterol promotes mitochondrial biogenesis, improves liver regeneration, and suppresses liver injury and inflammation after liver resection in mice with endotoxemia.International journal of physiology, pathophysiology and pharmacology · 2025Article
- Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia.Journal of neuroinflammation · 2024Article
- NF-κB p65 and TCF-4 interactions are associated with LPS-stimulated IL-6 secretion of macrophages.Biochemistry and biophysics reports · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Dissecting the mediating role of inflammatory factors in the interaction between metabolites and sepsis: insights from bidirectional Mendelian randomization.Frontiers in endocrinology · 2024Article
- GOLPH3 promotes endotoxemia-induced liver and kidney injury through Golgi stress-mediated apoptosis and inflammatory response.Cell death & disease · 2023Article
- Therapeutic targeting approach on epithelial-mesenchymal plasticity to combat cancer metastasis.Medical oncology (Northwood, London, England) · 2023Review
- High trophinin-associated protein expression predicts good survival in acute myeloid leukemia with normal cytogenetics.Cancer biomarkers : section A of Disease markers · 2023Article
- Article
- WNT signaling and cancer stemness.Essays in biochemistry · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endotoxemia, a type of sepsis caused by gram-negative bacterial endotoxin [i.e., lipopolysaccharide (LPS)], is associated with manifestations such as cytokine storm; failure of multiple organs, including the liver; and a high mortality rate. We investigated the effect and mechanism of action of LGK974, a Wnt signaling inhibitor, in mice with LPS-induced endotoxemia, an animal model of sepsis. LGK974 significantly and dose-dependently increased the survival rate and reduced plasma cytokine levels in mice with LPS-induced endotoxemia. Transcriptome analysis of liver tissues revealed significant changes in the expression of genes associated with the Wnt pathway as well as cytokine and NF-κB signaling during endotoxemia. LGK974 treatment suppressed the activation of NF-κB signaling and cytokine expression as well as the Wnt/β-catenin pathway in the livers of endotoxemic mice. Coimmunoprecipitation of phospho-IκB and β-transducin repeat-containing protein (β-TrCP) was increased in the livers of endotoxemic mice but was reduced by LGK974 treatment. Moreover, LGK974 treatment decreased the coimmunoprecipitation and colocalization of β-catenin and NF-κB, which were elevated in the livers of endotoxemic mice. Our results reveal crosstalk between the Wnt/β-catenin and NF-κB pathways via interactions between β-TrCP and phospho-IκB and between β-catenin and NF-κB during endotoxemia. The results of this study strongly suggest that the crosstalk between the Wnt/β-catenin and NF-κB pathways contributes to the mutual activation of these two pathways during endotoxemia, which results in amplified cytokine production, liver damage and death, and that LGK974 suppresses this vicious amplification cycle by reducing the crosstalk between these two pathways.
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