title: 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.
authors.affiliation: a Department of Biology , Faculty of Science, Istanbul University , 34134 Vezneciler, Istanbul , Turkey.
authors.forename: Oznur
authors.initials: O
authors.lastname: Yilmaz
authors.affiliation: a Department of Biology , Faculty of Science, Istanbul University , 34134 Vezneciler, Istanbul , Turkey.
authors.forename: Fusun
authors.initials: F
authors.lastname: Oztay
authors.affiliation: a Department of Biology , Faculty of Science, Istanbul University , 34134 Vezneciler, Istanbul , Turkey.
authors.forename: Ozgecan
authors.initials: O
authors.lastname: Kayalar
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D000069439:Dasatinib / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D000903:Antibiotics, Antineoplastic; D024042:Collagen Type I; D047428:Protein Kinase Inhibitors; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D000069439:Dasatinib
keywords: ERK1/2; PDGFR-α; Pulmonary fibrosis; c-Abl; dasatinib; fibroblasts