Impaired ciliogenesis in small airway epithelial cells involves in the development of idiopathic pulmonary fibrosis.

Accumulating evidence suggests that abnormalities in airway epithelial cells involve in the development of idiopathic pulmonary fibrosis (IPF). However, whether ciliary impairment contributes to IPF pathogenesis is unspecified. In this study, we evaluated the ciliogenesis potency of IPF-derived small airway epithelial cells (SAECs), assessed the effect of aberrant ciliogenesis on lung fibroblast activation and further identified whether improving ciliogenesis could attenuate pulmonary fibrosis. Here, we showed that upon external injury or serial cell passage, IPF-derived SAECs had greater decline in ciliogenesis potency as compared to healthy control (HC). Conditioned medium harvested from SAECs post injury, serial passage or silencing the ciliogenesis regulator FOXJ1 promoted the expression of α-smooth muscle actin (α-SMA) and fibronectin (FN) in human lung fibroblasts as compared to their corresponding controls. Mice with bleomycin (BLM)-induced lung fibrosis had reduced number of ciliated cells as compared to the saline control, while overexpressing Foxj1 in mouse lung attenuated the extent of pulmonary fibrosis. LY450139, a γ-secretase inhibitor, could also improve ciliogenesis in IPF-derived SAECs and inhibit lung fibroblast activation induced by ciliogenesis impairment. We demonstrated the contributing role of ciliogenesis impairment in IPF pathogenesis. Targeting the ciliogenesis abnormality may be a potential therapeutic strategy for IPF.