M10 peptide attenuates silica-induced pulmonary fibrosis by inhibiting Smad2 phosphorylation.

Silica-induced pulmonary fibrosis is a kind of worldwide occupational disease, and there is no effective treatment at present. Peptide therapy has attracted significant attention due to its simple structure, high selectiveness, strong bioactivity, relative safety, and high patient tolerance. In this study, we first confirmed that M10, a 10 amino acid peptide, has anti-fibrotic effects during the early and late stages of silica-induced fibrosis in mouse models and then partly explored the underlying mechanisms in vitro. M10 was detected in both the cell cytoplasm and nuclei. M10 showed no cytotoxicity to pulmonary epithelial cells and fibroblasts at the given concentrations. Functionally, M10 can reverse the silica-induced EMT process in epithelial cells and decrease TGF-β1-stimulated fibroblast activation. Further mechanism investigations supported that M10 can block TGF-β1 signalling by inhibiting phosphorylation of Smad2 protein in vitro and in vivo. All of the results indicate that M10 peptide may be a new method for the treatment of silica-induced pulmonary fibrosis. • M10 peptide prevents silica-induced pulmonary fibrosis in the early fibrotic stage. • M10 attenuates silica-induced pulmonary fibrosis in the late fibrotic stage. • M10 suppresses silica-induced EMT process of the pulmonary epithelial cells. • M10 inhibits TGF-β1-stimulated pulmonary fibroblast activation. • M10 downregulates the expression of phosphorylated Smad2 both in vitro and in vivo. [ABSTRACT FROM AUTHOR]