ArticleClinical science (London, England : 1979)2022
Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.
Article in Clinical science (London, England : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Multi-omics reveals fibroblast subtypes with distinct roles in inflammatory bowel disease.Biology direct · 2026Article
- Polystyrene-associated pulmonary fibrosis: a summary based on the available evidence and prospects.Frontiers in immunology · 2026Review
- Article
- The Wnt/β-Catenin Inhibitor HC-1 Suppresses Liver Fibrosis by Inhibiting Activated Hepatic Stellate Cells and Inducing Matrix Metalloproteinase-1.Yonago acta medica · 2025Article
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- Differential analysis of sorting nexin 10 and sterol regulatory element-binding protein 2 expression in inflammatory bowel disease.Immunologic research · 2024Article
- Phytochemical Compounds as Promising Therapeutics for Intestinal Fibrosis in Inflammatory Bowel Disease: A Critical Review.Nutrients · 2024Review
- The Role of WNT3A Protein and Gene Variants in Allergic Rhinitis: A Case-Control Study.Current issues in molecular biology · 2024Article
- Intestinal strictures in Crohn's disease: An update from 2023.United European gastroenterology journal · 2024Review
- Fibrostenosing Crohn's Disease: Pathogenetic Mechanisms and New Therapeutic Horizons.International journal of molecular sciences · 2024Review
- Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn's Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets.Journal of Crohn's & colitis · 2024Article
- Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn's disease.Journal of cellular and molecular medicine · 2024Article
- Prospective therapeutics for intestinal and hepatic fibrosis.Bioengineering & translational medicine · 2023Review
- Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor β1 (TGFβ) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. β-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFβ signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in β-catenin-positive cells. In vitro, activation of Wnt-β-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of β-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFβ increased β-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFβ up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a β-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFβ signalling pathways in CD intestinal fibrosis.
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