ArticleInternational journal of molecular sciences2021
WNT/β-Catenin Signaling Promotes TGF-β-Mediated Activation of Human Cardiac Fibroblasts by Enhancing IL-11 Production.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 0 citations in OpenAlex.
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- Matrifibrocytes Redefine Cardiac Fibrosis: From Terminal Differentiation to Translational Modulation.Journal of cellular and molecular medicine · 2026Review
- Exploring the Complexities of TGF-β Signaling in Keloids: Beyond the Classical Smad Pathway.International journal of molecular sciences · 2026Review
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- Advances in natural compounds modulating autophagy for the therapeutic intervention of heart failure.Molecular and cellular biochemistry · 2026Review
- TGF-β in chronic kidney disease: a controversy for decades.Frontiers in immunology · 2026Review
- CD73 activity controls cytotoxic CD4 T-cell response driving myocardial pathology in chronic Chagas disease.Frontiers in immunology · 2026Article
- Endothelial epigenetic senescence driven microglial activation mediates cardio-retinal neuroinflammation in heart failure.Theranostics · 2026Article
- Enhancement of Platinum-based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-induced Activation of the TGF-β1/β-Catenin Signaling Pathway.Current molecular medicine · 2026Article
- Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights.Genes · 2025Review
- Synovial Dysregulation in Ankle Osteoarthritis: Molecular Insights and Pathogenetic Pathways.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Reprogramming of Mitochondrial and Cellular Energy Metabolism in Fibroblasts and Cardiomyocytes: Mechanisms and Therapeutic Strategies in Cardiac Fibrosis.Journal of cardiovascular translational research · 2025Review
- Targeting the NO-sGC-cGMP Pathway: Mechanisms of Action of Vericiguat in Chronic Heart Failure.Cells · 2025Review
- Novel Interleukin-11 Inhibitors Attenuate Collagen Production in Patient-Derived Synovial Fibroblasts.Cureus · 2025Article
- Article
- Histone Deacetylase 6 Controls Atrial Fibrosis and Remodeling in Postinfarction Mice Through the Modulation of Wnt3a/GSK-3β Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Cardiac Fibroblasts: Helping or Hurting.Genes · 2025Review
- Protective Effects of SIRT2 Inhibition on Cardiac Fibrosis.Anatolian journal of cardiology · 2025Article
- Cancer-associated fibroblasts induce almonertinib resistance in non-small cell lung cancer.Journal of translational medicine · 2025Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cardiac fibrosis is a pathological process associated with the development of heart failure. TGF-β and WNT signaling have been implicated in pathogenesis of cardiac fibrosis, however, little is known about molecular cross-talk between these two pathways. The aim of this study was to examine the effect of exogenous canonical WNT3a and non-canonical WNT5a in TGF-β-activated human cardiac fibroblasts. We found that WNT3a and TGF-β induced a β-catenin-dependent response, whereas WNT5a prompted AP-1 activity. TGF-β triggered profibrotic signatures in cardiac fibroblasts, and co-stimulation with WNT3a or co-activation of the β-catenin pathway with the GSK3β inhibitor CHIR99021 enhanced collagen I and fibronectin production and development of active contractile stress fibers. In the absence of TGF-β, neither WNT3a nor CHIR99021 exerted profibrotic responses. On a molecular level, in TGF-β-activated fibroblasts, WNT3a enhanced phosphorylation of TAK1 and production and secretion of IL-11 but showed no effect on the Smad pathway. Neutralization of IL-11 activity with the blocking anti-IL-11 antibody effectively reduced the profibrotic response of cardiac fibroblasts activated with TGF-β and WNT3a. In contrast to canonical WNT3a, co-activation with non-canonical WNT5a suppressed TGF-β-induced production of collagen I. In conclusion, WNT/β-catenin signaling promotes TGF-β-mediated fibroblast-to-myofibroblast transition by enhancing IL-11 production. Thus, the uncovered mechanism broadens our knowledge on a molecular basis of cardiac fibrogenesis and defines novel therapeutic targets for fibrotic heart diseases.
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