MCTR1 Intervention Reverses Experimental Lung Fibrosis in Mice

PURPOSE: Pulmonary fibrosis (PF) is a progressing lethal disease, effective curative therapies remain elusive and mortality remains high. Maresin conjugates in tissue regeneration 1 (MCTR1) is a DHA-derived lipid mediator promoting inflammation resolution produced in macrophage. However, the effect of MCTR1 on PF remains unknown. MATERIAL AND METHODS: We established a lung fibrosis model in mice induced by intratracheal administration of bleomycin (BLM). On day 7 after lung fibrosis model establishment, treatment with MCTR1 up to day 21. The body weight of each mouse was recorded every day and survival curves were plotted. Histological staining was used to detect pulmonary inflammation and fibrosis. Lung sections were examined with transmission electron microscope to evaluate the ultrastructure of cells and deposit of collagen. Inflammatory cytokines in lung tissues were tested by ELISA. q-PCR and Western blot were used to evaluate the mRNA and the protein levels of EMT-related markers. RESULTS: We found that MCTR1 intervention attenuated BLM-induced lung inflammatory and fibrotic response. Furthermore, MCTR1 protected BLM-induced epithelial cell destroy and reversed epithelial-to-mesenchymal transition phenotype into an epithelial one in lung fibrosis mice. Most importantly, post-treatment with MCTR1 restored BLM-induced lung dysfunction and enhanced survival rate significantly. CONCLUSION: Posttreatment with MCTR1 attenuated BLM-induced inflammation and fibrosis changes in mice, suggested MCTR1 may serve as a novel therapeutic strategy for fibrosis-related diseases.