ArticleThe American journal of pathology2015
WNT5A inhibits hepatocyte proliferation and concludes β-catenin signaling in liver regeneration.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- p16Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Liver regeneration: unraveling the molecular mechanisms and clinical application.Journal of translational medicine · 2025Review
- Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.Regenerative therapy · 2025Review
- Wnt/CaOncology letters · 2025Review
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- SEL1L-HRD1 ER-associated degradation suppresses hepatocyte hyperproliferation and liver cancer.iScience · 2022Article
- Serum secreted frizzled-related protein 5 in relation to insulin sensitivity and its regulation by insulin and free fatty acids.Endocrine · 2021Article
- miR-20a/TCF4 axis-mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6.Journal of cellular and molecular medicine · 2021Article
- Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies.Oncology research · 2021Review
- Liver regeneration observed across the different classes of vertebrates from an evolutionary perspective.Heliyon · 2021Review
- Liver regeneration: biological and pathological mechanisms and implications.Nature reviews. Gastroenterology & hepatology · 2021Review
- Endothelial Wnts regulate β-catenin signaling in murine liver zonation and regeneration: A sequel to the Wnt-Wnt situation.Hepatology communications · 2018Article
- Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology.Annual review of pathology · 2018Review
- Article
- Review
- Sorting nexin 27 interacts with Fzd7 and mediates Wnt signalling.Bioscience reports · 2016Article
- Regenerating the liver: not so simple after all?F1000Research · 2016Review
- Role of β-catenin in development of bile ducts.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Activation of Wnt/β-catenin signaling during liver regeneration (LR) after partial hepatectomy (PH) is observed in several species. However, how this pathway is turned off when hepatocyte proliferation is no longer required is unknown. We assessed LR in liver-specific knockouts of Wntless (Wls-LKO), a protein required for Wnt secretion from a cell. When subjected to PH, Wls-LKO showed prolongation of hepatocyte proliferation for up to 4 days compared with littermate controls. This coincided with increased β-catenin-T-cell factor 4 interaction and cyclin-D1 expression. Wls-LKO showed decreased expression and secretion of inhibitory Wnt5a during LR. Wnt5a expression increased between 24 and 48 hours, and Frizzled-2 between 24 and 72 hours, after PH in normal mice. Treatment of primary mouse hepatocytes and liver tumor cells with Wnt5a led to a notable decrease in β-catenin-T-cell factor activity, cyclin-D1 expression, and cell proliferation. Intriguingly, Wnt5a-LKO did not display any prolongation of LR because of compensation by other cells. In addition, Wnt5a-LKO hepatocytes failed to respond to exogenous Wnt5a treatment in culture because of a compensatory decrease in Frizzled-2 expression. In conclusion, we demonstrate Wnt5a to be, by default, a negative regulator of β-catenin signaling and hepatocyte proliferation, both in vitro and in vivo. We also provide evidence that the Wnt5a/Frizzled-2 axis suppresses β-catenin signaling in hepatocytes in an autocrine manner, thereby contributing to timely conclusion of the LR process.
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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.