Abstract
Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.
Highlights
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation, fibrotic change of lung tissues and impaired lung function [1]
Epithelial–mesenchymal transition (EMT) of epithelial cells has been shown to be implicated in fibrotic lung diseases
To determine the role of kurarinone in pulmonary fibrosis, we examined the effect of kurarinone on TGF-β-induced epithelial–mesenchymal transition (EMT) in BEAS-2B human lung epithelial cells
Summary
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation, fibrotic change of lung tissues and impaired lung function [1]. The development of pulmonary fibrosis involves lung injury, inflammation, myofibroblast formation and accumulation of extracellular matrix (ECM). TGF-β induced epithelial–mesenchymal transition (EMT) of lung epithelial cells is recognized to play an important role in myofibroblast formation [12]. EMT of alveolar epithelial cells induced by TGF-β may be one of the important mechanisms in the development of pulmonary fibrosis. Kurarinone attenuates renal fibrosis via inhibiting the EMT of tubular epithelial cells [23]. Based on these reports, we investigated the role of kurarinone in pulmonary fibrosis using a bleomycin (BLM)-induced pulmonary fibrosis mouse model and explored the associated mechanisms
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