Fenbendazole Attenuates Bleomycin-induced Pulmonary Fibrosis in Mice via Suppression of Fibroblast-to-myofibroblast Differentiation

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease with unknown etiology. Despite substantial progress in our understanding of pulmonary fibrosis pathogenesis and drug development, there is still no cure for this devastating disease. Fenbendazole (FBZ) is a benzimidazole compound that is widely used as an anthelmintic agent and recent studies have expanded the scope of its pharmacological effects and application prospect. In this study, we demonstrated that FBZ treatment blunt bleomycin-induced lung fibrosis in mice. In vitro study showed that FBZ inhibited the proliferation and migration of human embryo lung fibroblasts. Further studies showed that FBZ significantly inhibited glucose consumption, moderated glycolytic metabolism in fibroblasts, thus activated adenosine monophosphate-activated protein kinase (AMPK), and reduced activation of mammalian target of rapamycin (mTOR) pathway, thereby inhibiting transforming growth factor-β (TGF-β1)-induced fibroblast-to-myofibroblast differentiation and collagen synthesis. In summary, our data suggested that FBZ has the potential as a novel treatment of pulmonary fibrosis and other fibrotic diseases.