TY - JOUR T1 - The effect of dasatinib, a novel tyrosine kinase inhibitor, on the regression of pulmonary fibrosis in mice JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3905 AU - Ozgecan Kayalar AU - Oznur Yilmaz AU - Fusun Oztay Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3905.abstract N2 - Pulmonary fibrosis (PF) is characterized by an increased in number of fibroblast/myofibroblast and excessive accumulation of extracellular matrix components. This study focused the first time the effects of dasatinib, a tyrosine kinase inhibitor, on the myofibroblast activation and the synthesis of collagen-I in mice lung with PF induced by bleomycine (BLM).PF was induced by intratracheal BLM instillation in mice. Adult mice were divided 4 groups: mice dissected after 21st days of the first BLM (0.08 mg/kg) injection (I) and their controls (II), mice treated with dasatinib (2 mg/kg) during one week after 14 days of the first BLM injection and dissected in the 21st days of experiment (III) and their controls (IV). Fibrosis score and myofibroblast activation were determined under microscope, while it was analyzed the expression of collagen-I, alpha-smooth muscle actin (α-SMA), phospho-platelet derivated growth factor receptor-alpha (p-PDGFR-α), phospho-Abelson kinase (c-Abl) and phospho-ERK by immunoblotting and qRT-PCR in the lung.BLM treatments resulted in increased in the fibroblast proliferation, expressions of collagen-I, α-SMA, p-PDGFR-α, p-ERK, and p–c-Abl in the fibrotic lung. These alterations in fibrotic lung were regressed by dasatinib. Thus it was decreased fibrosis score to 3 from 5. Dasatinib treatments were limited myofibroblast activation and collagen-I synthesis, by the inhibition of PDGFR-α and cytoplasmic c-Abl in PF. The present study represented the using of dasatinib as a novel tyrosine kinase inhibitor with anti-fibrotic effect in the regression of PF. ER -