Inhibition of bleomycin-induced pulmonary fibrosis in mice by the novel peptide EZY-1 purified from Eucheuma

Abstract

For the first time, a new 16-amino-acid peptide was isolated from Eucheuma, an edible seaweed, and named EZY-1. EZY-1 was used to interfere with bleomycin-induced mice pulmonary fibrosis. The target proteins of EZY-1 were screened by an in vitro pull-down method combined with LC-MS/MS. The results showed that EZY-1 can inhibit the idiopathic pulmonary fibrosis (IPF) induced by bleomycin. The potency and safety of EZY-1 are superior to those of the drug used for clinical treatment, pirfenidone. The results showed that EZY-1 suppresses the TGF-β/Smad, PI3K-Akt-mTOR, Rac1-PAK2-cAb1 and MAPK signal transduction pathways. Proteins such as ERK, Akt, PDGF receptor β, vitronectin, raptor and SHP2 exhibited binding to EZY-1 in an in vitro pull-down assay combined with LC-MS/MS analysis. EZY-1 was confirmed to be an effective component of Eucheuma in the inhibition of IPF. The signalling pathways and target proteins of EZY-1 were preliminarily predicted. This study lays the foundation for the development of new drugs from Eucheuma for the treatment of IPF.