Inhibition of MARCO ameliorates silica-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is linked to fibrosis following exposure to silica. The scavenger receptor, macrophage receptor with collagenous structure (MARCO) plays an important role in silica-induced inflammation, however, the effect of MARCO on silica-induced fibrosis has not been identified. We hypothesized that MARCO would regulate EMT and be involved in the development of silicosis. Herein, we found that MARCO was highly expressed in lung tissue after exposure to silica and a MARCO inhibitor PolyG could alleviate pulmonary fibrosis in vivo. Our results confirmed that the expression of epithelial marker such as E-cadherin decreased, while the expression of mesenchymal markers, including vimentin and α-SMA increased after silica treatment. Furthermore, PolyG administration efficiently blocked the mRNA and protein expression of EMT markers and decreased the level of fibrosis-related transcription factors and proteins, such as Col1a1, Col3a1, Collagen I and Collagen III in the lungs of silica-exposed rats. The findings demonstrate that the macrophage membrane receptor MARCO controls the fibrotic response through regulating EMT in experimental silicosis and suggest a novel target for preventive intervention.