ArticleRespiratory research2022
Amphiregulin induces CCN2 and fibronectin expression by TGF-β through EGFR-dependent pathway in lung epithelial cells.
Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
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- Stimulation of EGFR signaling in fibro-adipogenic precursors decreases adipogenesis in Duchenne muscular dystrophy.Skeletal muscle · 2026Article
- The Role of Aryl Hydrocarbon Receptor-Dependent Signaling Pathway in the Profibrotic Effects of Dioxin-like Compounds in Human Renal Tubular Epithelial Cells.Environment & health (Washington, D.C.) · 2026Article
- Epithelial-to-mesenchymal transition as a central driver of tumor cell plasticity.Nature cancer · 2026Review
- The network pharmacology prediction and experiment validation of Astragalus membranaceus for alleviating silicosis fibrosis via decreasing MMP9 and EGFR expression.Scientific reports · 2026Article
- Obstructive sleep apnea and lung cancer: molecular underpinnings and clinical translational prospects.Frontiers in cell and developmental biology · 2026Review
- Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis.Frontiers in medicine · 2026Review
- JNK inhibitor SP600125 alleviates TGF-β2-induced epithelial-mesenchymal transition in RPE cellInternational journal of ophthalmology · 2026Article
- Integrating Disease Data and Toxicology Studies to Uncover the Mechanisms of Indium Tin Oxide (ITO) Nanoparticle-Induced Pulmonary Fibrosis and Develop an Adverse Outcome Pathway (AOP) Framework.Environment & health (Washington, D.C.) · 2025Article
- The Effects and Mechanisms of the YY1/EGFR Axis on Inflammation and Oxidative Stress in Asthma.Cell biochemistry and biophysics · 2025Article
- Herbacetin Alleviates Influenza Virus-Induced Lung Injury and Fibrosis by Targeting the Neuraminidase Protein.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Amphiregulin and Fibrosis: Existing Evidence and Future Directions.International journal of molecular sciences · 2025Review
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- NR4A1 Mediates Bronchopulmonary Dysplasia-Like Lung Injury Induced by Intrauterine Inflammation in Mouse Offspring.International journal of molecular sciences · 2025Article
- Quercetin targets TGFβ-primed human MDA-MB-231 triple-negative breast cancer cells, linking epithelial-mesenchymal transition to cell senescence and fibrosis.Molecular biology reports · 2025Article
- Chelerythrine Inhibits TGF-β-Induced Epithelial-Mesenchymal Transition in A549 Cells via RRM2.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes.Life (Basel, Switzerland) · 2025Article
- TGF-β induces EMT in thyroid cancer cells by regulating transcription factors.Thyroid research · 2025Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAirway fibrosis is one of the pathological characteristics of severe asthma. Transforming growth factor (TGF)-β has been known to promote epithelial-mesenchymal transition formation and to play a role in the progression of tissue fibrosis. Cellular communication network factor 2 (CCN2) and fibronectin (FN) are well-known markers of EMT and fibrosis. However, whether AREG is involved in TGF-β-induced CCN2 and FN expression in human lung epithelial cells is unknown.
methodsAREG and FN were analyzed by immunofluorescence staining on ovalbumin-challenged mice. CCN2 and FN expression were evaluated in human lung epithelial (A459) cells following TGF or AREG treatment for the indicated times. Secreted AREG from A549 cells was detected by ELISA. Cell migration was observed by a wound healing assay. Chromatin immunoprecipitation was used to detect the c-Jun binding to the CCN2 promoter.
resultsAREG and FN expression colocalized in lung tissues from mice with ovalbumin-induced asthma by immunofluorescence staining. Moreover, TGF-β caused the release of AREG from A549 cells into the medium. Smad3 siRNA down-regulated AREG expression. AREG also stimulated CCN2 and FN expression, JNK and c-Jun phosphorylation, and cell migration in A549 cells. AREG small interfering (si) RNA inhibited TGF-β-induced expression of CCN2, FN, and cell migration. Furthermore, AREG-induced CCN2 and FN expression were inhibited by EGFR siRNA, a JNK inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). EGFR siRNA attenuated AREG-induced JNK and c-Jun phosphorylation. Moreover, SP600125 downregulated AREG-induced c-Jun phosphorylation.
conclusionThese results suggested that AREG mediates the TGF-β-induced EMT in human lung epithelial cells through EGFR/JNK/AP-1 activation. Understanding the role of AREG in the EMT could foster the development of therapeutic strategies for airway remodeling in severe asthma.
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