Entrectinib ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β1 signaling pathway.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease with lesions confined to the lungs and is prevalent in the middle-aged and elderly population. The average survival time after diagnosis of IPF is only 3-5years, and the mortality rate is higher than that of most tumours. IPF is called a "tumour-like disease". Entrectinib is a new oral formulation developed by Roche and was approved by the FDA to treat a wide variety of tumours. In this study, we explored the potential effects and mechanisms of entrectinib on pulmonary fibrosis in vitro and in vivo. In vivo studies showed that entrectinib is effective in alleviating bleomycin-induced pulmonary fibrosis. In vitro studies demonstrated that entrectinib dose-dependently inhibits TGF-β1/non-Smad signaling and attenuates TGF-β1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). In conclusion, entrectinib blocks TGF-β1-induced lung fibroblast activation and EMT and then attenuates bleomycin-induced pulmonary fibrosis in mice.