DDIT3 aggravates pulpitis by modulating M1 polarization through EGR1 in macrophages

Abstract

DNA damage-inducible transcript 3 (DDIT3), a stress response gene, engages in the physiological and pathological processes of organisms, whereas its impact on pulpitis has not been defined yet. It has been demonstrated that macrophage polarization has a significant impact on inflammation. This research intends to investigate the effect of DDIT3 on the inflammation of pulpitis and macrophage polarization. C57BL/6J mice were used to model experimental pulpitis at 6, 12, 24, and 72 h after pulp exposure, with untreated mice as the control. The progression of pulpitis was visible histologically, and DDIT3 showed a trend of initially upward and downward later. Compared with wild-type mice, inflammatory cytokines and M1 macrophages were reduced, while M2 macrophages were increased in DDIT3 knockout mice. In RAW264.7 cells and bone borrow-derived macrophages, DDIT3 was found to enhance M1 polarization while impair M2 polarization. Targeted knockdown of early growth response 1 (EGR1) could rescue the blocking effect of DDIT3 deletion on M1 polarization. In conclusion, our results indicated that DDIT3 could exacerbate inflammation of pulpitis through the regulation of macrophage polarization, and DDIT3 could promote M1 polarization by inhibiting EGR1. It provides a new target for pulpitis treatment and tissue regeneration in the future.