Maresin 1 inhibits transforming growth factor-β1-induced proliferation, migration and differentiation in human lung fibroblasts

The myofibroblast has been implicated to be an important pathogenic cell in all fibrotic diseases, through synthesis of excess extracellular matrix. Lung fibroblast migration, proliferation and differentiation into a myofibroblast-like cell type are regarded as important steps in the formation of lung fibrosis. In the present study, the effect of maresin 1 (MaR 1), a pro-resolving lipid mediator, on transforming growth factor (TGF)-beta 1-stimulated lung fibroblasts was investigated, and the underlying molecular mechanisms were examined. The results of the present study demonstrated that MaR 1 inhibited TGF-beta 1-induced proliferative and migratory ability, assessed using MTT and scratch wound healing assays. The TGF-beta 1-induced expression of alpha-smooth muscle actin (alpha-SMA) and collagen type I, the hallmarks of myofibroblast differentiation, was decreased by MaR 1 at the mRNA and protein levels, determined using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Immunofluorescence demonstrated that MaR 1 downregulated the TGF-beta 1-induced expression of alpha-SMA. In addition, phosphorylated mothers against decapentaplegic homolog 2/3 (Smad2/3) and extracellular signal-related kinases (ERK) 1/2 were upregulated in TGF-beta 1-induced lung fibroblasts, and these effects were attenuated by MaR 1 administration. In conclusion, the results of the present study demonstrated that MaR 1 inhibited the TGF-beta 1-induced proliferation, migration and differentiation of human lung fibroblasts. These observed effects may be mediated in part by decreased phosphorylation of Smad2/3 and ERK1/2 signaling pathways. Therefore, MaR 1 may be a potential therapeutic approach to lung fibrotic diseases.