Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation
Copyright © 2020. Published by Elsevier B.V..
Paraquat (PQ) poisoning-induced pulmonary fibrosis always results in fatal harm to patients. Our study aimed to investigate the functions of the Wnt/β-catenin pathway in PQ-induced pulmonary fibrosis. By comparing the proteomic profiles of rat lung tissues using protein array in the absence or presence of PQ, the Wnt/β-catenin signaling, as a fibrosis-related pathway, was discovered to be profoundly activated by PQ. The protein levels of Wnt/β-catenin signaling components including MMP-2, β-catenin, Wnt3a, Wnt10b, Cyclin D1, and WISP1 were increased in PQ-treated rat lung tissues. Surprisingly, PQ was found to be able to promote lung epithelial cells and fibroblasts differentiating into myofibroblasts by activating Wnt/β-catenin signaling pathway. Dickkopf-1 (DKK1), an antagonist of Wnt/β-catenin signaling pathway, could inhibit the myofibroblast differentiation and attenuate PQ-induced pulmonary fibrogenesis in vitro and in vivo. The expression levels of fibroblasts markers Vimentin, α-smooth muscle actin (α-SMA) and Collagen I was detected and found to be increased when PQ treated and restored with additional DKK1 treatment. In summary, these assays indicated that Wnt/β-catenin signaling pathway played a regulatory role in the differentiation of lung epithelial cells and fibroblasts, and the pathogenesis of pulmonary fibrosis related to PQ. Inhibition of the Wnt/β-catenin signaling pathway may be investigated further as a potential fibrosis suppressor for pulmonary fibrosis therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:333 |
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| Enthalten in: |
Toxicology letters - 333(2020) vom: 15. Okt., Seite 170-183 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Zhaorui [VerfasserIn] |
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| Links: |
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| Themen: |
Epithelial-mesenchymal transition |
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| Anmerkungen: |
Date Completed 02.11.2020 Date Revised 02.11.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.toxlet.2020.08.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313701458 |
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| 520 | |a Paraquat (PQ) poisoning-induced pulmonary fibrosis always results in fatal harm to patients. Our study aimed to investigate the functions of the Wnt/β-catenin pathway in PQ-induced pulmonary fibrosis. By comparing the proteomic profiles of rat lung tissues using protein array in the absence or presence of PQ, the Wnt/β-catenin signaling, as a fibrosis-related pathway, was discovered to be profoundly activated by PQ. The protein levels of Wnt/β-catenin signaling components including MMP-2, β-catenin, Wnt3a, Wnt10b, Cyclin D1, and WISP1 were increased in PQ-treated rat lung tissues. Surprisingly, PQ was found to be able to promote lung epithelial cells and fibroblasts differentiating into myofibroblasts by activating Wnt/β-catenin signaling pathway. Dickkopf-1 (DKK1), an antagonist of Wnt/β-catenin signaling pathway, could inhibit the myofibroblast differentiation and attenuate PQ-induced pulmonary fibrogenesis in vitro and in vivo. The expression levels of fibroblasts markers Vimentin, α-smooth muscle actin (α-SMA) and Collagen I was detected and found to be increased when PQ treated and restored with additional DKK1 treatment. In summary, these assays indicated that Wnt/β-catenin signaling pathway played a regulatory role in the differentiation of lung epithelial cells and fibroblasts, and the pathogenesis of pulmonary fibrosis related to PQ. Inhibition of the Wnt/β-catenin signaling pathway may be investigated further as a potential fibrosis suppressor for pulmonary fibrosis therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Wnt/β-catenin signaling pathway | |
| 650 | 4 | |a epithelial-mesenchymal transition | |
| 650 | 4 | |a myofibroblast differentiation | |
| 650 | 4 | |a paraquat poisoning | |
| 650 | 4 | |a pulmonary fibrosis | |
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| 650 | 7 | |a Paraquat |2 NLM | |
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| 700 | 1 | |a Wang, Mengmeng |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Changbao |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Shinan |e verfasserin |4 aut | |
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