Idiopathic pulmonary fibrosis (IPF), characterized by excessive
collagen deposition, is a progressive and typically fatal
lung disease without effective therapeutic strategies.
Juglanin, as a
natural product mainly isolated from green walnut husks of Juglans mandshuric, has various bioactivities, including anti-oxidative, anti-inflammatory and anti-fibrotic effects. Stimulator of
interferon genes (
Sting) is a signaling molecule and plays an essential role in meditating
fibrosis. However, the effects of Jug and
Sting on
pulmonary fibrosis are not fully understood. In this study, we investigated the role of Jug
in bleomycin (BLM)-induced
inflammation and
fibrosis mouse model, as well as the underlying molecular mechanism. The results here indicated that Jug-treated mice exhibited a definitively improved survival rate than that of the BLM-challenged mice. Jug administration significantly alleviated neutrophil alveolar infiltration, lung vascular permeability and pro-inflammatory response in BLM mice. Subsequently, the
pulmonary fibrosis induced by BLM was markedly attenuated by Jug through reducing the expression of fibrotic hallmarks, including transforming growth factor-β1 (TGF-β1),
fibronectin, matrix metallo-proteinase-9 (MMP-9), α-smooth muscle actin (α-SMA) and
collagen I. Importantly, we found that BLM mice showed higher expression levels of
Sting in lung tissues, which were notably restrained by Jug treatment. The role of Jug in suppressing
Sting was confirmed in TGF-β-incubated cells. Notably, the in vitro analysis further showed that
Sting knockdown could ameliorate TGF-β-triggered
collagen accumulation. In contrast, TGF-β-induced
fibrosis was accelerated by
Sting over-expression. Therefore, BLM may induce lung
fibrosis through activating
Sting signaling, and Jug could be used therapeutically to improve tissue repair and attenuate the intractable disease.