Pterostilbene Alleviates Pulmonary Fibrosis by Regulating ASIC2

Background: Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, and its current treatment have certain shortcomings and adverse effects. In this study, we evaluate the anti-fibrotic activity of pterostilbene (PTE) using an IPF model induced by TGF-β1 in vitro.Methods: A549 and AEC cells were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. 30 μmol/L PTE was used to treat the cells. The epithelial-mesenchymal transition (EMT), accumulation of extracellular matrix (ECM) and autophagy of cells were suggested by western blot. The apoptosis was proved by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1+PTE) was performed, and differentially expressed genes caused by PTE were identified. The ASIC2 overexpression plasmid was used to rescue the protein level of ASIC2 in A549 and AEC cells.Results: TGF-β1 caused the EMT and accumulation of ECM, and blocked the autophagy and apoptosis of A549 and AEC cells. Most importantly, 30 μmol/L PTE inhibited the pulmonary fibrosis induced by TGF-β1. Compared with cells treated with TGF-β1, PTE treatment inhibited the EMT and accumulation of ECM, and rescued cell apoptosis and autophagy. The results of transcriptome high-throughput sequencing performed that PTE greatly reduced the protein level of ASIC2. In addition, compared with the TGF-β1+PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and accumulation of ECM, and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by down-regulating ASIC2. Conclusions: In conclusion, our study suggests that PTE and ASIC2 inhibitors may benefit future IPF treatments.