Related Experiment Video
Updated: Mar 29, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice
Oznur Yilmaz1, Fusun Oztay1, Ozgecan Kayalar1
1a Department of Biology , Faculty of Science, Istanbul University , 34134 Vezneciler, Istanbul , Turkey.
Abstract:
Anti-fibrotic effect of dasatinib, a platelet-derived growth factor receptor (PDGFR) and Src-kinase inhibitor, was tested on pulmonary fibrosis (PF). Adult mice were divided into four groups: mice dissected 21 d after the bleomycin (BLM) instillation (0.08 mg/kg in 200 µl) (I) and their controls (II), and mice treated with dasatinib (8 mg/kg in 100 µl, gavage) for one week 14 d after BLM instillation and dissected 21 d after instillation (III) and their controls (IV). The fibrosis score and the levels of fibrotic markers were analyzed in lungs. BLM treatment-induced cell proliferation and increased the levels of collagen-1, alpha smooth muscle actin, phospho (p)-PDGFR-alpha, p-Src, p-extracellular signal-regulated kinases1/2 and p-cytoplasmic-Abelson-kinase (c-Abl) in lungs, and down-regulated PTEN expression. Dasatinib reversed these alterations in the fibrotic lung. Dasatinib limited myofibroblast activation and collagen-1 accumulation by the inhibition of PDGFR-alpha, and Src and c-Abl activations. In conclusion, dasatinib may be a novel tyrosine and Src-kinase inhibitor for PF regression in mice.
Insights
Dasatinib, a drug targeting platelet-derived growth factor receptor (PDGFR) and Src-kinase, demonstrated anti-fibrotic effects in a mouse model of pulmonary fibrosis (PF). It reversed bleomycin-induced lung damage by inhibiting key fibrotic pathways.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Cell Biology
Background:
- Pulmonary fibrosis (PF) is a progressive lung disease with limited treatment options.
- Platelet-derived growth factor receptor (PDGFR) and Src-kinase signaling pathways are implicated in fibrotic processes.
Purpose of the Study:
- To investigate the anti-fibrotic potential of dasatinib, a dual PDGFR and Src-kinase inhibitor, in a bleomycin-induced pulmonary fibrosis mouse model.
Main Methods:
- Adult mice received bleomycin (BLM) instillation to induce pulmonary fibrosis.
- Mice were treated with dasatinib or vehicle control.
- Lung fibrosis scores and fibrotic marker levels (collagen-1, alpha-smooth muscle actin, phospho-PDGFR-alpha, phospho-Src, phospho-ERK1/2, phospho-c-Abl, PTEN) were analyzed.
Main Results:
- BLM treatment led to increased cell proliferation, collagen-1, alpha-smooth muscle actin, and activation of PDGFR-alpha, Src, ERK1/2, and c-Abl, while down-regulating PTEN.
- Dasatinib treatment reversed these BLM-induced alterations.
- Dasatinib inhibited myofibroblast activation and collagen-1 accumulation by suppressing PDGFR-alpha, Src, and c-Abl activation.
Conclusions:
- Dasatinib exhibits significant anti-fibrotic effects in a mouse model of pulmonary fibrosis.
- Dasatinib's mechanism involves the inhibition of PDGFR-alpha, Src, and c-Abl signaling pathways.
- Dasatinib represents a potential novel therapeutic agent for pulmonary fibrosis regression.
