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Abstract Title:

Pterostilbene alleviates pulmonary fibrosis by regulating ASIC2.

Abstract Source:

Chin Med. 2021 Jul 28 ;16(1):66. Epub 2021 Jul 28. PMID: 34321072

Abstract Author(s):

Yanfang Peng, Yingwen Zhang, Yabing Zhang, Xiuping Wang, Yukun Xia

Article Affiliation:

Yanfang Peng

Abstract:

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, but its current treatment has certain shortcomings and adverse effects. In this study, we evaluate the antifibrotic activity of pterostilbene (PTE) using an in vitro IPF model induced by transforming growth factor (TGF)-β1.

METHODS: A549 and alveolar epithelial cells (AECs) were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. Then, 30 μmol/L of PTE was used to treat these cells. The epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and autophagy in cells were evaluated by western blot. Apoptosis was validated by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing was performed on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1 + PTE), and differentially expressed genes in PTE-treated cells were identified. The acid sensing ion channel subunit 2 (ASIC2) overexpression plasmidwas used to rescue the protein levels of ASIC2 in A549 and AECs.

RESULTS: TGF-β1 caused EMT and ECM accumulation, and blocked the autophagy and apoptosis of A549 and AECs. Most importantly, 30 μmol/L of PTE inhibited pulmonary fibrosis induced by TGF-β1. Compared with TGF-β1, PTE inhibited EMT and ECM accumulation and rescued cell apoptosis and autophagy. The results oftranscriptome high-throughput sequencing revealed that PTE greatly reduced the protein level of ASIC2. Compared with the TGF-β1 + PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and ECM accumulation and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by downregulating ASIC2.

CONCLUSIONS: This study suggests that PTE and ASIC2 inhibitors may have potential as IPF treatments in the future.

Study Type : In Vitro Study

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