Abstract
Pulmonary fibrosis (PF) is a progressive respiratory disease. Phycocyanin derived eicosapeptide (PP20) is a novel peptide derived from active protein C-phycocyanin in Cyanobacteria. The aim of our study was to explore the anti-fibrotic activity of the PP20 and its underlying mechanism. Characteristic features of pulmonary fibrosis in oleic acid (OA)-induced mice and epithelial-mesenchymal transition (EMT) in TGF-β1-exposed A549 and HFL-1 cells with or without PP20 and the change of TGF-β/Smad and MAPK signaling pathways were examined. Smad and MAPK agonists were used to explore the role of TGF-β/Smad and MAPK signaling in TGF-β1- induced collagen I expression in A549 cells and α-SMA expression in HFL-1 cells when treated with PP20. Our results showed that PP20 significantly alleviated the inflammatory response and tissue destruction, inhibited EMT, restored the imbalance of TIMP-1/MMP-9 and reduced collagen fiber deposition. Moreover, PP20 inhibited TGF-β1-induced EMT and collagen I expression in A549 cells. PP20 could also inhibit the proliferation, and decrease TGF-β1-induced the expression of collagen I and transformation of fibroblasts into myofibroblasts in HFL-1 cells. Additionally, animal experiments and cell experiments combined with pathway agonists have shown that PP20 can negatively regulate TGF-β/Smad and MAPK pathways and show anti-fibrotic properties. PP20 may be a promising drug candidate for protection against pulmonary fibrosis.