Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice

Yilmaz O., Oztay F., Kayalar O.

GROWTH FACTORS, cilt.33, ss.366-375, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33
  • 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: Pulmonary fibrosis, dasatinib, PDGFR-alpha, c-Abl, fibroblasts, ERK1/2, TYROSINE KINASE INHIBITOR, INDUCED LUNG FIBROSIS, SRC FAMILY KINASES, GROWTH-FACTOR, IMATINIB MESYLATE, C-ABL, MYOFIBROBLAST DIFFERENTIATION, TGF-BETA, FIBROBLASTS, EXPRESSION
  • İstanbul 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 21d after the bleomycin (BLM) instillation (0.08mg/kg in 200 mu l) (I) and their controls (II), and mice treated with dasatinib (8mg/kg in 100 mu l, gavage) for one week 14d after BLM instillation and dissected 21d 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.