ArticleArthritis and rheumatism2012
Wnt/β-catenin signaling is hyperactivated in systemic sclerosis and induces Smad-dependent fibrotic responses in mesenchymal cells.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.
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
121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.The Journal of investigative dermatology · 2017Trial
- Therapeutic potential of astrocyte transdifferentiated neurons.Neural regeneration research · 2026Article
- Pulmonary parenchyma becomes a self-organized dissipative structure in lung cancers and pulmonary inflammatory diseases.Physiological reports · 2026Article
- [Role of the TGFZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Systemic sclerosis, main culprits and involved signaling pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- Antifibrotic effects of specific targeting of the 5-hydroxytryptamine 2B receptor (5-HTArthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Wnt Activation in Mature Dermal Adipocytes Leads to Lipodystrophy and Skin Fibrosis via ATGL-Dependent Lipolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Cardiac Fibroblasts: Helping or Hurting.Genes · 2025Review
- Single-cell and molecular insights into the immunopathogenic mechanisms of oral mucous membrane pemphigoid.Computational and structural biotechnology journal · 2025Article
- ADAM Metallopeptidase domain 19 promotes skin fibrosis in systemic sclerosis via neuregulin-1.Molecular medicine (Cambridge, Mass.) · 2024Article
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- Pathogenesis of interstitial lung disease in systemic sclerosis.Rheumatology and immunology research · 2024Article
- Understanding Fibrous Tissue in the Effective Healing of Rotator Cuff Injury.Journal of surgery and research · 2024Article
- Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.Current rheumatology reviews · 2024Review
- C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis.Communications biology · 2023Article
- IL-6 trans-signaling in a humanized mouse model of scleroderma.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Role of Autophagy and Apoptosis in Affected Skin and Lungs in Patients with Systemic Sclerosis.International journal of molecular sciences · 2023Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveFibrosis in human diseases and animal models is associated with aberrant Wnt/β-catenin pathway activation. The aim of this study was to characterize the regulation, activity, mechanism of action, and significance of Wnt/β-catenin signaling in the context of systemic sclerosis (SSc).
methodsThe expression of Wnt signaling pathway components in SSc skin biopsy specimens was analyzed. The regulation of profibrotic responses by canonical Wnt/β-catenin was examined in explanted human mesenchymal cells. Fibrotic responses were studied using proliferation, migration, and gel contraction assays. The cell fate specification of subcutaneous preadipocytes by canonical Wnt signaling was evaluated.
resultsAnalysis of published genome-wide expression data revealed elevated expression of the Wnt receptor FZD2 and the Wnt target LEF1 and decreased expression of Wnt antagonists DKK2 and WIF1 in skin biopsy specimens from subsets of patients with diffuse cutaneous SSc compared to the other distinct subsets. Immunohistochemical analysis showed increased nuclear β-catenin expression in these biopsy specimens. In vitro, Wnt-3a induced β-catenin activation, stimulated fibroblast proliferation and migration, collagen gel contraction, and myofibroblast differentiation, and enhanced profibrotic gene expression. Genetic and pharmacologic approaches were used to demonstrate that these profibrotic responses involved autocrine transforming growth factor β signaling via Smads. In contrast, in explanted subcutaneous preadipocytes, Wnt-3a repressed adipogenesis and promoted myofibroblast differentiation.
conclusionCanonical Wnt signaling was hyperactivated in SSc skin biopsy specimens. In explanted mesenchymal cells, Wnt-3a stimulated fibrogenic responses while suppressing adipogenesis. Taken together, these results indicate that Wnts have potent profibrotic effects, and that canonical Wnt signaling plays an important role in the pathogenesis of fibrosis and lipoatrophy in SSc.
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.