Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

• Main Authors: Fei Gao (Author), Yun Zhang (Author), Zhizhou Yang (Author), Mengmeng Wang (Author), Zhiyi Zhou (Author), Wei Zhang (Author), Yi Ren (Author), Xiaoqin Han (Author), Mei Wei (Author), Zhaorui Sun (Author), Shinan Nie (Author)
• Format: Book
• Published: Frontiers Media S.A., 2020-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) in vivo and in vitro. Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.

Item Description

1663-9812
10.3389/fphar.2020.584098