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

Abstract

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.

• Authors: Yan Li, Xiaoming Ji, Wenxi Yao, Honghong Pan, Ping Li, Yi Liu, Jiali Yuan, Qi Xu, Chunhui Ni
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 376 Pg. 46-57 (08 01 2019) ISSN: 1096-0333 [Electronic] United States
• PMID: 31125577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• M10 peptide
• Peptides
• Smad2 Protein
• Smad2 protein, mouse
• Transforming Growth Factor beta1
• Silicon Dioxide

Topics

• Animals
• Cell Line
• Disease Models, Animal
• Epithelial Cells
• Epithelial-Mesenchymal Transition (drug effects)
• Fibroblasts (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Peptides (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Pulmonary Fibrosis (chemically induced, drug therapy)
• Signal Transduction (drug effects)
• Silicon Dioxide (toxicity)
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism, pharmacology)