CSF3 a New Therapeutic Target for Pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by worsening lung function with dyspnea and leading to the death within approximately 3 years.1 Because IPF-specific therapies still have not been developed, early recognition, accurate diagnosis, and effective treatment for IPF are urgently needed. Here, we found that CSF3 is increased in human IPF tissue and in the bleomycin induced mouse lung fibrosis model, which induces transdifferentiation of lung epithelial cells to myofibroblasts, consequently promoting lung fibrosis through enriching ECM components. Our results revealed that Akt signaling pathway induces expression of CSF3 and CSF3, acting as an autocrine factor, activates Stat3 to induce epithelial to mesenchymal transition (EMT) of lung epithelial cells. Surprisingly, CSF3 neutralizing antibodies completely block advanced fibrosis and reverse the fibrotic lungs to normal conditions in lung fibrosis mouse model. Collectively, our results demonstrated that CSF3 is a major regulator of IPF through EMT of lung epithelial cells and blockade of CSF3 may reverse the fibrosis by facilitating deactivation of myofibroblasts. This study suggests that CSF3 as a potential therapeutic target to restore progressive fibrotic disorders