ArticleCell death & disease2021
Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 38 citations in OpenAlex.
- GRAIL-heart: A graph attention network for inferring ligand-receptor interactions in spatial transcriptomics.MethodsX · 2026Article
- RNA-Binding Proteins Regulate Cardiovascular Disease Progression Through Alternative Splicing and Alternative Polyadenylation.Journal of cardiovascular translational research · 2026Review
- Multiple triggering mechanisms of myocardial fibrosis: Comparison and integration in different disease contexts.iScience · 2026Review
- Intercellular chemerin-cmklr1 couples epicardial mechanosensing to fibroblasts in pressure overload.Nature communications · 2026Article
- Wnt11 mediates fibroblast-smooth muscle cell interaction to promote neurogenic bladder fibrosis in rats.Communications biology · 2026Article
- Persistent Wnt/β-catenin signaling disables soft palatogenesis and palatal osteogenesis by inducing mesenchymal condensation.Frontiers in cell and developmental biology · 2026Article
- CKAP4 Promotes Atrial Fibrosis and Enhances Atrial Fibrillation Vulnerability via WNT/β-Catenin Activation.Circulation. Arrhythmia and electrophysiology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Targeting WNT5A noncanonical signaling attenuates renal fibrosis progression in acute kidney injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Multidimensional excavation of the current status and trends of mechanobiology in cardiovascular homeostasis and remodeling within 20 years.Mechanobiology in medicine · 2025Review
- UHRF1-mediated epigenetic reprogramming regulates glycolysis to promote progression of B-cell acute lymphoblastic leukemia.Cell death & disease · 2025Article
- Role and Mechanism of Lamellar Derived Growth Factor /AKT Pathway in Ventricular Remodeling Induced by Pressure Overload.Cell biochemistry and biophysics · 2025Article
- Targeting Wnt Pathways with Small Molecules as New Approach in Cardiovascular Disease.Current cardiology reviews · 2025Review
- Hypertrophic cardiomyopathy-associated mutations drive stromal activation via EGFR-mediated paracrine signaling.Science advances · 2024Article
- Article
- Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.Journal of neuroinflammation · 2024Article
- Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop.Cell death & disease · 2024Article
- Wilforine inhibits rheumatoid arthritis pathology through the Wnt11/β-catenin signaling pathway axis.Arthritis research & therapy · 2023Article
- Epigenetic Regulation of Fibroblasts and Crosstalk between Cardiomyocytes and Non-Myocyte Cells in Cardiac Fibrosis.Biomolecules · 2023Review
- Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Progressive cardiac fibrosis accelerates the development of heart failure. Here, we aimed to explore serum Wnt5a and Wnt11 levels in hypertension patients, the roles of Wnt5a and Wnt11 in cardiac fibrosis and potential mechanisms under pressure overload. The pressure overload mouse model was built by transverse aortic constriction (TAC). Cardiac fibrosis was analyzed by Masson's staining. Serum Wnt5a or Wnt11 was elevated and associated with diastolic dysfunction in hypertension patients. TAC enhanced the expression and secretion of Wnt5a or Wnt11 from cardiomyocytes (CMs), cardiac fibroblasts (CFs), and cardiac microvascular endothelial cells (CMECs). Knockdown of Wnt5a and Wnt11 greatly improved cardiac fibrosis and function at 4 weeks after TAC. In vitro, shWnt5a or shWnt11 lentivirus transfection inhibited pro-fibrotic effects in CFs under mechanical stretch (MS). Similarly, conditional medium from stretched-CMs transfected with shWnt5a or shWnt11 lentivirus significantly suppressed the pro-fibrotic effects induced by conditional medium from stretched-CMs. These data suggested that CMs- or CFs-derived Wnt5a or Wnt11 showed a pro-fibrotic effect under pressure overload. In vitro, exogenous Wnt5a or Wnt11 activated ERK and p38 (fibrotic-related signaling) pathway, promoted the phosphorylation of EGFR, and increased the expression of Frizzled 5 (FZD5) in CFs. Inhibition or knockdown of EGFR greatly attenuated the increased FZD5, p-p38, and p-ERK levels, and the pro-fibrotic effect induced by Wnt5a or Wnt11 in CFs. Si-FZD5 transfection suppressed the increased p-EGFR level, and the fibrotic-related effects in CFs treated with Wnt5a or Wnt11. In conclusion, pressure overload enhances the secretion of Wnt5a or Wnt11 from CMs and CFs which promotes cardiac fibrosis by activation the crosstalk of FZD5 and EGFR. Thus, Wnt5a or Wnt11 may be a novel therapeutic target for the prevention of cardiac fibrosis under pressure overload.
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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.