IJMS, Vol. 23, Pages 11707: PEG2-Induced Pyroptosis Regulates the Expression of HMGB1 and Promotes hEM15A Migration in Endometriosis (International Journal of Molecular Sciences)

Endometriosis (EMS) is a common gynecological disease. Prostaglandin E2 (PGE2), which induces chronic pelvic inflammation and cell pyroptosis, a form of programmed cell death based on inflammasome activation, are involved in EMS, but the extent of their involvement and roles remain unclear. The present study aimed to evaluate PGE2-induced pyroptosis in EMS and the influence of PGE2 in EMS progression. Using western blotting, it was found that the expressions of PGE2 and pyroptosis-related proteins (NLRP3, cleaved caspase-1, interleukin (IL)-1β and IL-18) were higher in EMS tissues than in normal endometrial tissues. The levels of PGE2, IL-1β, and IL-18 in the serum of patients with EMS and cell culture fluids were also detected. Using the transwell assay, we verified that PGE2 promoted hEM15A migration via the NLRP3/caspase-1 pyroptotic pathway, and PGE2-induced pyroptosis upregulated the expressions of high mobility group box 1 (HMGB1), E-cadherin, and vimentin. Immunohistochemistry analysis confirmed that PGE2-induced pyroptosis contributed to EMS invasion. These results suggest that PGE2-induced pyroptosis affects the progression of EMS by changing the migration ability of pyroptotic cells and upregulating the expression of HMGB1, E-cadherin, and vimentin. Our findings provide crucial evidence for new treatment pathways and use of anti-inflammatory drugs in EMS.