ArticleThe Journal of biological chemistry2012
Amphiregulin, an epidermal growth factor receptor ligand, plays an essential role in the pathogenesis of transforming growth factor-β-induced pulmonary fibrosis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 137 citations in OpenAlex.
- Safety and Pharmacokinetics of SRN001, a Novel siRNA Drug Targeting Amphiregulin via the SAMiRNA Platform.Drug design, development and therapy · 2026Trial
- Effect of Xinjiang UyghurBioMed research international · 2016Trial
- Chitinase 3-like-1 and its receptors in Hermansky-Pudlak syndrome-associated lung disease.The Journal of clinical investigation · 2015Trial
- Decoding the Cellular Response to Methylthioadenosine Uncovers Novel Targets for Chronic Liver Disease.Cells · 2026Article
- Review
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.Nature immunology · 2026Article
- Human lung γδ T cells maintain functionality during inflammatory lung disease.bioRxiv : the preprint server for biology · 2026Article
- Milk fat globule EGF and factor V/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis.Scientific reports · 2026Article
- Oxymatrine Inhibits Epithelial-Mesenchymal Transition to Alleviate Airway Remodeling in Chronic Obstructive Pulmonary Disease by Suppressing the TGF-β1/Smad Pathway.The Kaohsiung journal of medical sciences · 2026Article
- IL1βJournal of translational medicine · 2026Article
- Regenerating myofiber with activating of TGF-β signaling contributes to macrophage efferocytosis through enhancing Tregs response in inflamed muscle.Frontiers in immunology · 2026Article
- Review
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.bioRxiv : the preprint server for biology · 2025Article
- Macrophage-derived amphiregulin induces myofibroblast transition in adipogenic lineage precursors near Staphylococcus aureus abscess in bone marrow.Nature communications · 2025Article
- Amphiregulin and Fibrosis: Existing Evidence and Future Directions.International journal of molecular sciences · 2025Review
- Generation of a novel lung fibrosis model using precision-cut lung slices from transgenic TGFβ1 mice.American journal of physiology. Cell physiology · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Systemic toxicity and toxicokinetics study of self-assembled-micelle inhibitory RNA-targeting amphiregulin in cynomolgus monkeys following intravenous injection.Toxicological research · 2025Article
- Lapatinib ameliorates skin fibrosis by inhibiting TGF-β1/Smad and non-Smad signaling pathway.Scientific reports · 2025Article
- Efficacy of epidermal growth factor in suppressing inflammation and proliferation in pterygial fibroblasts through interactions with microenvironmental M1 macrophages.Scientific reports · 2024Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated amphiregulin (AR) expression and EGR receptor (EGFR) activation have been described in animal models of pulmonary fibrosis and in patients with idiopathic pulmonary fibrosis. However, the exact role of AR in the pathogenesis of pulmonary fibrosis has not been clearly defined. Here, we show that a potent profibrogenic cytokine TGF-β1 significantly induced the expression of AR in lung fibroblasts in vitro and in murine lungs in vivo. AR stimulated NIH3T3 fibroblast cell proliferation in a dose-dependent manner. Silencing of AR expression by siRNA or chemical inhibition of EGFR signaling, utilizing AG1478 and gefitinib, significantly reduced the ability of TGF-β1 to stimulate fibroblast proliferation and expression of α-smooth muscle actin, collagen, and other extracellular matrix-associated genes. TGF-β1-stimulated activation of Akt, ERK, and Smad signaling was also significantly inhibited by these interventions. Consistent with these in vitro findings, AR expression was impressively increased in the lungs of TGF-β1 transgenic mice, and either siRNA silencing of AR or chemical inhibition of EGFR signaling significantly reduced TGF-β1-stimulated collagen accumulation in the lung. These studies showed a novel regulatory role for AR in the pathogenesis of TGF-β1-induced pulmonary fibrosis. In addition, these studies suggest that AR, or AR-activated EGFR signaling, is a potential therapeutic target for idiopathic pulmonary fibrosis associated with TGF-β1 activation.
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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.