Enhanced β-Catenin/Foxo1 Activity Alleviates Pulmonary Fibrosis by Inhibiting β-Catenin/T Cell Factor Signaling

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, resulting in chronic respiratoryfailure and eventually death. β -catenin/Foxo1 showed a protective property in kidney fibrosis, but the role of β -catenin/Foxo1 in IPF was unclear. Our study aimed to investigate the role of β -catenin/Foxo1 in IPF and explore its underlying mechanism. The IPF model was established by injection of bleomycin (BLM) in vivo and stimulation by TGF- β 1 in MRC5 cell in vitro. Haematoxylin-eosin staining and Masson’s trichrome staining were performed to examine histopathological injury in lung. Protein expression of corresponding genes was detected using western blot. Immunofluorescence staining assay was carried out to detect the expression of β -catenin, Foxo1, TCF and α -SMA. The expression levels of inflammatory cytokines were determined using ELISA kit assay. The results showed that BLM induced a serious pulmonary injury and proliferated fibroblasts. A higher interaction of β -catenin with TCF and a lower interaction of β -catenin with Foxo1 was found in BLM group compared to the control group. TGF- β 1 promoted β -catenin/TCF, whereas ICG-001 inhibited β -catenin/TCF, and promoted β -catenin/Foxo1. Furthermore, ICG-001 reversed TGF- β 1 induced largely production of inflammatory cytokines and accumulation of extracellular matrix, as well as high expression of α -SMA. However, AS1842856, a FOXO1 antagonist, strengthened the effects induced by TGF- β 1. In summary, our study revealed that β -catenin/Foxo1 protected against IPF through inhibiting inflammatory response and extracellular matrix accumulation, providing an alternative approach to explain the potential mechanism of IPF and seek for more effective therapeutic drugs.