ArticleLung2016
Methotrexate-Induced Epithelial-Mesenchymal Transition in the Alveolar Epithelial Cell Line A549.
Article in Lung, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Emerging mechanistic trends and clinical efficacy for methotrexate: Applications to inflammatory bowel disease.Pharmacological reviews · 2026Review
- Article
- Role of Interleukin-6 in Rheumatoid Arthritis-Associated Interstitial Lung Disease: Focus on the JAK/STAT Pathway and Macrophage Polarization.Journal of inflammation research · 2025Review
- Quercetin and Nano-Derivatives: Potential and Challenges in Cancer Therapy.International journal of nanomedicine · 2025Review
- Role of Small Airway Epithelial-Mesenchymal Transition and CXCL13 in Pulmonary Lymphoid Follicle Formation in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2024Article
- Impact of Janus kinase inhibitors and methotrexate on interstitial lung disease in rheumatoid arthritis patients.Frontiers in immunology · 2024Article
- Dihydromyricetin Modulates Nrf2 and NF-κB Crosstalk to Alleviate Methotrexate-Induced Lung Toxicity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells.Toxicological research · 2022Article
- Animal models of drug-induced pulmonary fibrosis: an overview of molecular mechanisms and characteristics.Cell biology and toxicology · 2022Review
- Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis.Nature communications · 2022Article
- Differential mechanisms underlying methotrexate-induced cell death and epithelial-mesenchymal transition in A549 cells.Toxicological research · 2021Article
- Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition.Biomolecules · 2021Review
- Impact of Differentiated Macrophage-Like Cells on the Transcriptional Toxicity Profile of CuO Nanoparticles in Co-Cultured Lung Epithelial Cells.International journal of molecular sciences · 2021Article
- Effect of transforming growth factor-β1 on functional expression of monocarboxylate transporter 1 in alveolar epithelial A549 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Total extract of Xin Jia Xuan Bai Cheng Qi decoction inhibits pulmonary fibrosis via the TGF-β/Smad signaling pathways in vivo and in vitro.Drug design, development and therapy · 2019Article
- p38 MAPK is Crucial for Wnt1- and LiCl-Induced Epithelial Mesenchymal Transition.Current medical science · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMethotrexate (MTX) therapy of certain cancers and rheumatoid arthritis often induces serious interstitial lung complications including pulmonary fibrosis. In this study, we investigated the epithelial-mesenchymal transition (EMT) induced by MTX and by transforming growth factor (TGF)-β1 in the human alveolar epithelial cell line A549 in order to develop new strategies for the prevention of EMT.
methodsFirst, we examined the effect of TGF-β1 and MTX on cell morphology and the expression of EMT-related mRNAs in A549 cells. Then, the effects of SB431542 (SB), a potent inhibitor of TGF-β receptor kinase, and a neutralizing antibody for TGF-β1 on the phenotypic changes of A549 cells induced by TGF-β1 and MTX were examined.
resultsAfter incubation with TGF-β1 and MTX, the mRNA expression of epithelial markers such as cytokeratin 19 was reduced, while that of mesenchymal markers such as α-smooth muscle actin was increased. SB suppressed the development of morphological changes and partially rescued alterations in mRNA expression of EMT markers induced by MTX. In addition, the enhancement of SMAD2 phosphorylation by MTX was also prevented by SB. On the other hand, EMT-related changes induced by MTX were not affected by a neutralizing antibody for TGF-β1.
conclusionWe have demonstrated that phenotypic changes of A549 cells induced by MTX are partly mediated by a TGF-β1-related intracellular signaling pathway, although TGF-β1 itself is not directly involved in this process.
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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.