Therapeutic effects of scavenger receptor MARCO ligand on silica-induced pulmonary fibrosis in rats.

Pharmacological targeting of MARCO with polyG (MARCO inhibitor) attenuated the silica-induced fibrosis through suppressing the ERS-associated apoptosis and inhibiting the EMT process. • ERS was involved in silica-induced pulmonary fibrosis. • Therapeutic administration of polyG alleviated silica-induced pulmonary fibrosis in rats. • Antagonism of scavenger receptor MARCO reduced ERS-related apoptosis and EMT in silica-exposed rats. Pulmonary fibrosis induced by prolonged exposure to silica particles is a chronic and irreversible lung disease without effective treatment till now. Our previous study has shown that early intervention with MARCO antagonist PolyG could alleviate pulmonary fibrosis in silica-exposed rats. However, the therapeutic effects of PolyG on silica-induced pulmonary fibrosis have rarely been reported. In this study, we explored the effects of administration (on the 28th day after silica exposure) of PolyG (MARCO inhibitor) on an established rat silicosis model. The lungs were analyzed histopathologically in rats using HE and Masson staining. The silica-induced ERS-related apoptosis, EMT and fibrosis were evaluated using western blotting, qRT-PCR and immunohistochemical analyses. The results suggested that silica exposure could increase the MARCO activity, and induce ERS and EMT in lung tissues. Pharmacological targeting of MARCO with PolyG attenuated the development of pulmonary fibrosis in silica-exposed rats. Further study indicated that PolyG could inhibit silica-induced ERS-related apoptosis and EMT process. Together, our findings reveal an essential function of ERS-related apoptosis and EMT in the processes of pulmonary fibrosis caused by silica, and identify MARCO as a potential therapeutic pharmacological target for silicosis. [ABSTRACT FROM AUTHOR]