MiR-503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica-induced pulmonary fibrosis.

Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differentiation, are essential to explore therapeutic strategies. Our previous research showed that the up-regulation of miR-503 alleviated silica-induced pulmonary fibrosis in mice. In this study, we investigated whether miR-503 can regulate the TGF-β1-induced effects in lung fibroblasts. Mimic-based strategies aiming at up-regulating miR-503 were used to discuss the function of miR-503 in vivo and in vitro. We found that the expression level of miR-503 was decreased in fibroblasts stimulated by TGF-β1, and the up-regulation of miR-503 reduced the release of fibrotic factors and inhibited the migration and invasion abilities of fibroblasts. Combined with the up-regulation of miR-503 in a mouse model of silica-induced pulmonary fibrosis, we revealed that miR-503 mitigated the TGF-β1-induced effects in fibroblasts by regulating VEGFA and FGFR1 and then affecting the MAPK/ERK signalling pathway. In conclusion, miR-503 exerted protective roles in silica-induced pulmonary fibrosis and may represent a novel and potent candidate for therapeutic strategies in silicosis.