PT  - JOURNAL ARTICLE
AU  - Motoyasu Kato
AU  - Fumiyuki Takahashi
AU  - Shigehiro Yagishita
AU  - Tetsuhiko Asao
AU  - Ryota Kanemaru
AU  - Kentaro Suina
AU  - Hario Bascoro
AU  - Fariz Nurwidya
AU  - Isao Kobayashi
AU  - Keiko Muraki
AU  - Tadashi Sato
AU  - Naoko Shimada
AU  - Motomi Takahashi
AU  - Kazuhisa Takahashi
TI  - Dasatinib suppresses TGFβ-induced epithelial mesenchymal transition and inhibits pulmonary fibrosis
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P742
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P742.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P742.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - [Background] Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been reported that imatinib attenuated bleomycin (BLM)-induced fibrosis in mice. Dasatinib (DAS) is tyrosine kinase inhibitor against platelet derived growth factor receptor as well as imatinib. However, there have been no studies on the effects of DAS on pulmonary fibrosis. [Aim] Our aim is to investigate the effect of DAS on TGFβ-induced EMT in human alveolar epithelial cells in vitro and to evaluate the efficacy of DAS on lung fibrosis in vivo.[Materials and Methods] A549 cells were stimulated with TGFβ and treated with or without DAS. We analyzed epithelial and mesenchymal markers by quantitative real time PCR and western blot and cell motility by wound healing assay. We developed a mouse model for pulmonary fibrosis by intravenous injection of BLM. Either DAS or vehicle was administered by oral gavage, and mice were sacrificed on day 22. We evaluated pathological findings and measured the collagen contents in the lungs of the mice. [Results] In vitro, TGFβ-induced expression of mesenchymal proteins and transcriptional factors were significantly suppressed by the treatment with DAS. Furthermore, DAS markedly inhibited TGFβ-induced cell motility. In vivo, treatment with DAS significantly attenuated BLM-induced lung fibrosis and collagen contents in the lungs. [Conclusion] These findings suggest that DAS inhibits pulmonary fibrosis by suppressing TGFβ-induced EMT. DAS may be a promising and novel anti-fibrotic agent for the prevention of IPF.