ArticleNature medicine2017
ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 166 citations in OpenAlex.
- Photothermal-magnetic dual-activated Janus dressing for microenvironment purification and wireless electrically triggered healing with reduced scar formation.Bioactive materials · 2027Article
- Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).International journal of molecular medicine · 2026Review
- Breast cancer, fibrotic signalling, and development of atrial fibrillation.European heart journal · 2026Article
- Identifying novel druggable targets and repurposable drugs for premature ovarian insufficiency by integrated multiomics and causal inference analysis.GeroScience · 2026Article
- Kaempferol-modified mesenchymal stem cell extracellular vesicle-mimetics promote photoaging repair by suppressing ADAM10.Cell communication and signaling : CCS · 2026Article
- Gene expression and histological assessment of capsular fibrosis in post-traumatic shoulder stiffness following plate fixation of proximal humeral fractures: an exploratory pilot study.BMC musculoskeletal disorders · 2026Article
- EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation ResponseEndocrine, metabolic & immune disorders drug targets · 2026Article
- Harmine Derivative H-2-104 Alleviates Echinococcus granulosus-Induced Pulmonary Fibrosis in Mice by Inhibiting Fibroblast Activation and Inducing DNA Damage.Journal of immunology research · 2026Article
- Targeting Macrophage-to-Myofibroblast Transition Mitigates Progression from Inflammation to Fibrosis in Rosacea.International journal of biological sciences · 2026Article
- Identification of Ephrin type-B receptor 4 as a critical mediator of tissue fibrosis.JCI insight · 2025Article
- Idiopathic Pulmonary Fibrosis: Cellular Heterogeneity, Mechanisms, and Therapeutic Implications.MedComm · 2025Review
- Low circulating miR-190a-5p predicts progression of chronic kidney disease.Nature communications · 2025Article
- Durotaxis is a driver and potential therapeutic target in lung fibrosis and metastatic pancreatic cancer.Nature cell biology · 2025Article
- Proteomic Biomarkers of Survival in Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Disease.American journal of respiratory and critical care medicine · 2025Article
- EphrinB2 alleviates tubulointerstitial fibrosis in diabetic kidney disease.Journal of translational medicine · 2025Article
- Aging-associated interleukin-11 drives the molecular mechanism and targeted therapy of idiopathic pulmonary fibrosis.European journal of medical research · 2025Review
- A Disintegrin and Metalloproteinase 10 Regulates Ephrin B2-Mediated Endothelial Cell Sprouting and Ischemic Retinopathy.The American journal of pathology · 2025Article
- Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms.BMC medical genomics · 2025Article
- Inhibition of EphA2 by syndecan-4 in wounded skin regulates clustering of fibroblasts.Journal of molecular cell biology · 2025Article
- Mechanosensitive Piezo1 channel is highly expressed in the age-induced fibrotic uterus.Molecular biology reports · 2025Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodeling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however, the molecular mediators of myofibroblast activation have yet to be fully identified. Here we identify soluble ephrin-B2 (sEphrin-B2) as a new profibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of sEphrin-B2 promotes fibroblast chemotaxis and activation via EphB3 and/or EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a disintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 expression is increased by transforming growth factor (TGF)-β1, and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1-induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10-sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors EphB3 and EphB4 and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases.
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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.