Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice

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.

• Pulmonary fibrosis
• dasatinib
• PDGFR-α
• c-Abl
• fibroblasts
• ERK1/2

Acknowledgements

The p-ERK1/2 primary antibody has been presented by Damla Erdogan. We express our sincere thanks to her.

Declaration of interest

This study was funded by the Scientific Research Project Coordination Unit of Istanbul University (Grant numbers 22360 and 27653). Also, it was benefited from tools purchased by the other project (Grant number: 3319).

The coauthors do not have a conflict of interest. The analysis of qRT-PCR was performed by Ozgecan Kayalar.