A TSP-1 synthetic peptide inhibits bleomycin-induced lung fibrosis in mice.

Abstract

Bleomycin showed toxicity to lung and was recognized to induce a well model of lung fibrosis. Activated alveolar macrophages released increased amounts of transforming growth factor-beta1(TGF-beta1) in response to bleomycin-induced lung injury. Thrombospondin-1(TSP-1) was involved in the activation of latent TGF-beta1(L-TGF-beta1) through the association of the TSP-1/L-TGF-beta1 complex with the cell receptor of TSP-1, CD36. The antagonistic effects of the synthetic peptides were studied by the administration of TSP-1 (447-452) synthetic peptides to the mouse model. The hydroxyproline contents of the TSP-1-treated groups were significantly lower than those of other experimental groups. Inflammation, fibrotic degree and distribution of collagen fibers in the interstitial and alveolar in the TSP-1-treated groups were less than those of the other experimental groups. The expressions of collagen I and III in TSP-1-treated groups were significantly lower than in the other experimental groups. TSP-1 synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the model, resulting in the decreased severity of bleomycin-induced lung injury.