Abstract
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.
Highlights
Paraquat (PQ) is a fast-acting and non-selective contact herbicide that has been used in more than 120 countries since the 1960s (Dinis-Oliveira RJ et al, 2008)
We found that PQ could induce pulmonary fibrosis and epithelial-mesenchymal transition (EMT) through activating Wnt signal pathway, and ATG, as an active substance of Fructus Arctii, could attenuate PQ-induced EMT both in vivo and in vitro
We investigated the EMT in PQinduced lung fibrosis, and whether ATG could attenuate pulmonary fibrosis by alleviating EMT progress
Summary
Paraquat (PQ) is a fast-acting and non-selective contact herbicide that has been used in more than 120 countries since the 1960s (Dinis-Oliveira RJ et al, 2008). Its use has been banned or severely restricted, PQ self-poisoning is still frequent. It is reported the number of suicide attempts did not change after the ban in 2007 in France (Kervégant et al, 2013), and approximately 20% of the farmers continue to use PQ regardless of the ban in Korea (Bang et al, 2017). Respiratory failure is a predominant cause of PQ-induced death, because PQ, once ingested, accumulates in the lung through the polyamine uptake system
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