Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice
Growth Factors, cilt.33, sa.5-6, ss.366-375, 2015 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 33 Sayı: 5-6
- Basım Tarihi: 2015
- Doi Numarası: 10.3109/08977194.2015.1109511
- Dergi Adı: Growth Factors
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.366-375
- Anahtar Kelimeler: C-Abl, Dasatinib, ERK1/2, Fibroblasts, PDGFR-α, Pulmonary fibrosis
- Çukurova Üniversitesi Adresli: Evet
Özet
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.