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Disulfiram Alleviates MTX-Induced Pulmonary Fibrosis by Inhibiting EMT in Type 2 Alveolar Epithelial Cells
Xiaohui Wu1, Hong Xu2, Zhaohua Zhang3
1Clinical Medical School, Xi'an Medical University, Xi'an, 710021, Shaanxi, China. wuxh@xiyi.edu.cn.
Lung
|November 27, 2024
Summary
Disulfiram (DSF) can alleviate methotrexate (MTX)-induced pulmonary fibrosis by reducing inflammation and fibrotic markers. This study suggests DSF as a potential therapeutic for MTX-induced lung injury.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Toxicology
Background:
- Methotrexate (MTX) is a chemotherapy agent that can cause severe pulmonary fibrosis.
- Current treatments for MTX-induced pulmonary fibrosis are limited, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To investigate the potential of disulfiram (DSF) in mitigating MTX-induced pulmonary fibrosis.
- To elucidate the underlying molecular mechanisms of DSF's protective effects against MTX-induced lung injury.
Main Methods:
- Mice and MLE12 cells were treated with MTX and/or DSF.
- Lung tissues and cells were analyzed for fibrosis, inflammation, and epithelial-mesenchymal transition (EMT) markers using histological staining, qPCR, ELISA, and Western blot.
- RNA sequencing and bioinformatics analysis were performed to identify affected signaling pathways.
Main Results:
- DSF treatment significantly reduced MTX-induced pulmonary fibrosis, inflammation (IL-1β, TNF-α), and fibrotic markers (Col1α1, α-SMA, hydroxyproline).
- RNA-seq indicated that DSF modulates pathways involved in extracellular matrix remodeling.
- DSF partially restored E-cadherin expression and reduced α-SMA, suggesting inhibition of EMT.
Conclusions:
- Disulfiram alleviates MTX-induced pulmonary fibrosis, likely by inhibiting EMT in type 2 alveolar epithelial cells.
- DSF demonstrates potential as a therapeutic agent for managing MTX-induced lung toxicity.
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