Figure 8.

The schematic model for TIM-4 in macrophages mediates TGF-β1 secretion via the ROS/p38 MAPK/Egr-1 pathway to regulate nasal polyp formation. The increased production of TIM-4 in macrophages is stimulated by inflammatory microenvironment of CRSwNP. TIM-4 boosts the activity of the secondary messenger ROS. The activation of ROS promotes P38 MAPK phosphorylation and then increases the transcriptional activity of Egr-1. The cascade increases the transcription and translation of TGF-β1 in macrophages, resulting in an increase of TGF-β1 secretion, which culminates in promoted EMT in nasal epithelial cells. In conclusion, both increased accumulation of macrophages and increased TIM-4 production by macrophages may result in ROS-dependent activation of p38/MAPK/Egr-1 cascade, which contributes to nasal polyp formation.