Krupple-like-factor 4 Attenuates Lung Fibrosis via Inhibiting Epithelial-mesenchymal Transition

Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krupple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis. Transgenic mice with overexpression of KLF4 were subjected to bleomycin-induced pulmonary fibrosis model and showed attenuated lung fibrosis and EMT compared to wild type group. Furthermore, the effects overexpression and knockdown of KLF4 on TGF-beta 1-induced EMT were examined in AECs. Adenovirus-mediated overexpression of KLF4 attenuated TGF-beta 1-induced EMT and activation of Smad2/3 and Dvl in AECs. Conversely, knockdown of KLF4 promoted the activation of pathways above mentioned and TGF-beta 1-induced EMT. Our results demonstrates that KLF4 plays an important role in bleomycin-induced lung fibrosis through suppressing TGF beta 1-induced EMT. Thus, it may serve as a potential target for the treatment of pulmonary fibrosis.