ArticleHepatology (Baltimore, Md.)2020
Wnt/β-Catenin Signaling Plays a Protective Role in the Mdr2 Knockout Murine Model of Cholestatic Liver Disease.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Machine Learning-Based Models to Predict Drug-Induced Liver Injury (DILI) to Assist Medicinal Chemistry.Journal of medicinal chemistry · 2026Review
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- Loss of β-catenin in cholangiocytes promotes hepatocyte reprogramming and vascular remodeling during murine cholestasis.Cell communication and signaling : CCS · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Isovalerylspiramycin I alleviates liver injury and liver fibrosis by targeting the nucleotide-binding protein 2 (NUBP2)-vascular non-inflammatory molecule-1 (VNN1) pathway.Journal of pharmaceutical analysis · 2025Article
- Tetrahedral framework nucleic acids ameliorate cholestatic liver disease by activating Wnt/β-catenin signaling and promoting ERK1/2 phosphorylation.Regenerative biomaterials · 2025Article
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- Live-cell imaging of human liver fibrosis using hepatic micro-organoids.JCI insight · 2024Article
- Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.Hepatology communications · 2024Article
- Article
- Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model.Cell & bioscience · 2024Article
- MiR-22-3p and miR-29a-3p synergistically inhibit hepatic stellate cell activation by targeting AKT3.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- New and Emerging Research on Solute Carrier and ATP Binding Cassette Transporters in Drug Discovery and Development: Outlook From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence.Scientific reports · 2022Article
- Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities.Signal transduction and targeted therapy · 2022Review
- Role and Regulation of Wnt/β-Catenin in Hepatic Perivenous Zonation and Physiological Homeostasis.The American journal of pathology · 2022Review
- Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update.Journal of clinical and translational hepatology · 2021Review
- Review
- Dual β-Catenin and γ-Catenin Loss in Hepatocytes Impacts Their Polarity through Altered Transforming Growth Factor-β and Hepatocyte Nuclear Factor 4α Signaling.The American journal of pathology · 2021Article
- Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsThe Wnt/β-catenin signaling pathway has a well-described role in liver pathobiology. Its suppression was recently shown to decrease bile acid (BA) synthesis, thus preventing the development of cholestatic liver injury and fibrosis after bile duct ligation (BDL). APPROACH AND
resultsTo generalize these observations, we suppressed β-catenin in Mdr2 knockout (KO) mice, which develop sclerosing cholangitis due to regurgitation of BA from leaky ducts. When β-catenin was knocked down (KD) in KO for 2 weeks, hepatic and biliary injury were exacerbated in comparison to KO given placebo, as shown by serum biochemistry, ductular reaction, inflammation, and fibrosis. Simultaneously, KO/KD livers displayed increased oxidative stress and senescence and an impaired regenerative response. Although the total liver BA levels were similar between KO/KD and KO, there was significant dysregulation of BA transporters and BA detoxification/synthesis enzymes in KO/KD compared with KO alone. Multiphoton intravital microscopy revealed a mixing of blood and bile in the sinusoids, and validated the presence of increased serum BA in KO/KD mice. Although hepatocyte junctions were intact, KO/KD livers had significant canalicular defects, which resulted from loss of hepatocyte polarity. Thus, in contrast to the protective effect of β-catenin KD in BDL model, β-catenin KD in Mdr2 KO aggravated rather than alleviated injury by interfering with expression of BA transporters, hepatocyte polarity, canalicular structure, and the regenerative response.
conclusionsThe resulting imbalance between ongoing injury and restitution led to worsening of the Mdr2 KO phenotype, suggesting caution in targeting β-catenin globally for all cholestatic conditions.
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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.