Related Experiment Video
Updated: Jun 9, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin
Ping Wang1, Qing Tian, Zhi-xin Liang
1Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Background:
Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated. However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction. This study investigated the effect of gefitinib on lung fibrosis in mice.
Methods:
We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib. C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline. Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.
Results:
The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells. In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens I and III.
Conclusions:
These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.
Insights
Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, prevented lung fibrosis in a mouse model. This suggests EGFR inhibitors may treat pulmonary fibrosis by inhibiting mesenchymal cell proliferation.
Area of Science:
- Pharmacology
- Oncology
- Pulmonary Medicine
Background:
- Gefitinib (EGFR tyrosine kinase inhibitor) treats epithelial tumors like NSCLC.
- Clinical trials indicate gefitinib can cause lung fibrosis, a severe adverse reaction.
- This study investigated gefitinib's impact on bleomycin-induced lung fibrosis in mice.
Purpose of the Study:
- To investigate the effect of gefitinib on the development of lung fibrosis.
- To determine if gefitinib can prevent or mitigate pulmonary fibrosis.
- To explore the potential of EGFR tyrosine kinase inhibitors in treating lung fibrosis.
Main Methods:
- A mouse model of bleomycin-induced lung fibrosis was established.
- Mice received intratracheal bleomycin and/or intragastric gefitinib.
- Lung tissues were analyzed histologically and genetically at 14 and 21 days.
Main Results:
- Bleomycin successfully induced lung fibrosis.
- Gefitinib treatment prevented lung fibrosis and suppressed S100A4-positive fibroblast proliferation.
- Gefitinib reduced phosphorylated EGFR (p-EGFR) expression and inhibited collagen I and III accumulation.
Conclusions:
- Gefitinib mitigates bleomycin-induced pulmonary fibrosis in mice.
- Small molecule EGFR tyrosine kinase inhibitors show potential for preventing pulmonary fibrosis.
- Targeting tyrosine kinase receptors may offer a therapeutic strategy for human pulmonary fibrosis.
