Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways

Background Pirfenidone (PFD) is effective for pulmonary fibrosis (PF), but its action mechanism has not been fully explained. This study explored the signaling pathways involved in anti-fibrosis role of PFD, thus laying a foundation for clinical application. Methods Pulmonary fibrosis mice models were constructed by bleomycin (BLM), and TGF-beta 1 was used to treat human fetal lung fibroblasts (HLFs). Then, PFD was added into treated mice and cells alone or in combination with beta-catenin vector. The pathological changes, inflammatory factors levels, and Collagen I levels in mice lung tissues were assessed, as well as the activity of HLFs was measured. Levels of indices related to extracellular matrix, epithelial-mesenchymal transition (EMT), Wnt/GSK-3 beta/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways were determined in tissues or cells. Results After treatment with BLM, the inflammatory reaction and extracellular matrix deposition in mice lung tissues were serious, which were alleviated by PFD and aggravated by the addition of beta-catenin. In HLFs, PFD reduced the activity of HLFs induced by TGF-beta 1, inhibited levels of vimentin and N-cadherin and promoted levels of E-cadherin, whereas beta-catenin produced the opposite effects to PFD. In both tissues and cells, Wnt/GSK-3 beta/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways were activated, which could be suppressed by PFD. Conclusions PFD alleviated pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3 beta/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways, which might further improve the action mechanism of anti-fibrosis effect of PFD.