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Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation.
- Source :
-
Toxicology Letters . Oct2020, Vol. 333, p170-183. 14p. - Publication Year :
- 2020
-
Abstract
- • PQ induces myofibroblasts differentiation of lung epithelial cells and fibroblasts to promote pulmonary fibrosis. • PQ activates Wnt/β-catenin signaling pathway in pulmonary fibrogenesis. • DKK1 suppresses the myofibroblasts differentiation and ameliorates pulmonary fibrosis via inhibiting Wnt/β-catenin signaling. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03784274
- Volume :
- 333
- Database :
- Academic Search Index
- Journal :
- Toxicology Letters
- Publication Type :
- Academic Journal
- Accession number :
- 146535251
- Full Text :
- https://doi.org/10.1016/j.toxlet.2020.08.004