Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.584098
Keywords
paraquat; pulmonary fibrosis; arctigenin; epithelial-mesenchymal transition; Wnt3a/beta-catenin pathway
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Funding
- Social Development Projects of Jiangsu Province [BE2017720]
- Science Foundation of Jiangsu Health Commission [H2018039]
- National Natural Science Foundation of China [81401583, 81701894]
- Jiangsu Provincial Medical Youth Talent [QNRC2016909, QNRC2016908]
- Natural Science Foundation of Jiangsu Province [BK20190247]
- China Postdoctoral Science Foundation [2018M643890]
- Jiangsu Postdoctoral Science Foundation [2018K048A]
- Science Research and Technology Development General Program of Wuxi Health Commission, China [MS201714]
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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 alpha-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/beta-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/beta-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/beta-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.
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