SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model

- We found silica induced EMT and the activity of p38 MAPK in vivo.
- SB203580 could inhibit EMT and pulmonary fibrosis in silicosis model.
- P38 MAPK/ZEB-1 (ZEB-2, Twist) was involved at 7 days after silica instillation.

To investigate the role of p38 MAPK in silicosis, we explored the effects of SB203580 as a specific inhibitor of p38 MAPK in the silicosis model in rats. Rats were exposed to 50 mg/ml silica intratracheally. From the first day after instillation, rats were injected with SB203580 1 mg/kg/d. Rats were sacrificed at 7 and 15 days after exposure of silica. The results demonstrated SB203580 could prevent the activation of p38. TGF-β1 in bronchoalveolar lavage fluid, the expression of vimentin and α-SMA in the lung tissue was down-regulated and E-cadherin was up-regulated after intervention with SB203580 at 7 days and 15 days. The percentage of the cells staining with SP-C and vimentin doubly was lower in SB203580 treated group than in silica group at 7 days and 15days. SB203580 also inhibited the increase of ZEB-1, ZEB-2 and Twist at 7 days. Histopathologic examination showed the decrease in the number of nodules and the blue areas of collagen fibers in the lung after SB203580 treatment. The content of hydroxyproline and the expression of collagen I and III decreased in SB203580 treated group than in silica group. These results suggested that p38 MAPK/ZEB-1 (ZEB-2, Twist) pathway was involved at 7 days after silica instillation and p38 MAPK was pivotal for EMT in silicosis fibrosis in rats.

p38 MAPK was pivotal for EMT in silicosis fibrosis in rats. At 7 days after silica instillation, p38 MAPK/ZEB-1 (ZEB-2, Twist) was involved in EMT and pulmonary fibrosis, while SB203580 could inhibit the activity of p38 MAPK/ZEB-1 (ZEB-2, Twist) pathway by restraining the phosphorylation of MK-2.41