Prostaglandin E2 drives cellular senescence and scar fibrosis after cesarean section in mice

In a new mouse model of cesarean section scar defects, researchers investigated the mechanisms that disrupt uterine healing. The team combined metabolomics, transcriptomics, and functional assays to track scar formation. They found that increased activity of the PGES and prostaglandin E2 (PGE2) axis drives pathological tissue remodeling. High PGE2 levels trigger early senescence in macrophages. These senescent immune cells then relay pro-senescent signals to uterine fibroblasts through the IL-1β/IL-1R signaling pathway. This cellular relay prompts persistent fibroblast activation and progressive fibrosis, damaging the structure and function of the uterus. When investigators blocked the PGES/PGE2 pathway or applied anti-aging strategies in mice, fibrotic scarring decreased significantly. These interventions restored coordinated healing across both myometrial and endometrial layers of the uterus.