ArticleAmerican journal of respiratory and critical care medicine2013
Syndecan-2 exerts antifibrotic effects by promoting caveolin-1-mediated transforming growth factor-β receptor I internalization and inhibiting transforming growth factor-β1 signaling.
Article in American journal of respiratory and critical care medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Research on the role and mechanism of SLC7A5 in idiopathic pulmonary fibrosis.Molecular medicine reports · 2026Article
- Syndecan-2 Regulates Integrin-β1 to Influence the Abnormal Subchondral Bone in Early-stage Knee Osteoarthritis.Applied biochemistry and biotechnology · 2026Article
- Unveiling CCL2 and CXCL1: Key biomarkers and therapeutic targets in idiopathic pulmonary fibrosis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025Article
- Curated and harmonised transcriptomics datasets of interstitial lung diseases.Data in brief · 2025Article
- GPR40 activation alleviates pulmonary fibrosis by repressing M2 macrophage polarization through the PKD1/CD36/TGF-β1 pathway.Acta pharmacologica Sinica · 2025Article
- Macrophage subtypes and pathways in autoimmune interstitial lung diseases: potential therapeutic targets.Frontiers in immunology · 2025Article
- PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.PloS one · 2024Article
- Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts.Scientific reports · 2022Article
- Targeting Asporin in Lung Fibrosis: A New Approach to an Old Concept.American journal of respiratory cell and molecular biology · 2022Article
- Syndecan-2 enriches for hematopoietic stem cells and regulates stem cell repopulating capacity.Blood · 2022Article
- Mesenchymal stromal cell-derived syndecan-2 regulates the immune response during sepsis to foster bacterial clearance and resolution of inflammation.The FEBS journal · 2022Article
- CD148 Deficiency in Fibroblasts Promotes the Development of Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- How Do We Know What We Are Missing? Loss of Signaling through CD148 Drives Fibroblast Activation in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- The Cardiac Syndecan-2 Interactome.Frontiers in cell and developmental biology · 2020Article
- Palmitic Acid-Rich High-Fat Diet Exacerbates Experimental Pulmonary Fibrosis by Modulating Endoplasmic Reticulum Stress.American journal of respiratory cell and molecular biology · 2019Article
- Lung Adenocarcinoma Syndecan-2 Potentiates Cell Invasiveness.American journal of respiratory cell and molecular biology · 2019Article
- Macrophage PPAR-γ suppresses long-term lung fibrotic sequelae following acute influenza infection.PloS one · 2019Article
- Membrane TLR9 Positive Neutrophil Mediated MPLA Protects Against Fatal Bacterial Sepsis.Theranostics · 2019Article
- MicroRNA-708-3p as a potential therapeutic target via the ADAM17-GATA/STAT3 axis in idiopathic pulmonary fibrosis.Experimental & molecular medicine · 2018Article
- Syndecan-2 Attenuates Radiation-induced Pulmonary Fibrosis and Inhibits Fibroblast Activation by Regulating PI3K/Akt/ROCK Pathway via CD148.American journal of respiratory cell and molecular biology · 2018Article
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
rationaleAlveolar transforming growth factor (TGF)-β1 signaling and expression of TGF-β1 target genes are increased in patients with idiopathic pulmonary fibrosis (IPF) and in animal models of pulmonary fibrosis. Internalization and degradation of TGF-β receptor TβRI inhibits TGF-β signaling and could attenuate development of experimental lung fibrosis.
objectivesTo demonstrate that after experimental lung injury, human syndecan-2 confers antifibrotic effects by inhibiting TGF-β1 signaling in alveolar epithelial cells.
methodsMicroarray assays were performed to identify genes differentially expressed in alveolar macrophages of patients with IPF versus control subjects. Transgenic mice that constitutively overexpress human syndecan-2 in macrophages were developed to test the antifibrotic properties of syndecan-2. In vitro assays were performed to determine syndecan-2-dependent changes in epithelial cell TGF-β1 signaling, TGF-β1, and TβRI internalization and apoptosis. Wild-type mice were treated with recombinant human syndecan-2 during the fibrotic phase of bleomycin-induced lung injury. MEASUREMENTS AND MAIN
resultsWe observed significant increases in alveolar macrophage syndecan-2 levels in patients with IPF. Macrophage-specific overexpression of human syndecan-2 in transgenic mice conferred antifibrotic effects after lung injury by inhibiting TGF-β1 signaling and downstream expression of TGF-β1 target genes, reducing extracellular matrix production and alveolar epithelial cell apoptosis. In vitro, syndecan-2 promoted caveolin-1-dependent internalization of TGF-β1 and TβRI in alveolar epithelial cells, which inhibited TGF-β1 signaling and epithelial cell apoptosis. Therapeutic administration of human syndecan-2 abrogated lung fibrosis in mice.
conclusionsAlveolar macrophage syndecan-2 exerts antifibrotic effects by promoting caveolin-1-dependent TGF-β1 and TβRI internalization and inhibiting TGF-β1 signaling in alveolar epithelial cells. Hence, molecules that facilitate TβRI degradation via endocytosis represent potential therapies for pulmonary fibrosis.
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