Chemokine CCL21 promotes the pathological progression of endometriosis by regulating inflammatory cytokine expression and activating the NF-κB signaling pathway

Abstract Endometriosis, affecting approximately 10% of reproductive-aged women worldwide, is a typical chronic inflammatory disease. Inflammation-related genes (IRGs) play a crucial role in the occurrence and progression of various diseases, including endometriosis. However, identifying which IRGs affect the pathology of endometriosis and how to target them for treatment remains highly challenging. In the present study, the ectopic endometrium (EcE) and eutopic endometrium (EuE) from endometriosis patients were collected and a mouse model of endometriosis was established to investigate the expression levels of inflammatory factors. Three hub IRGs (CCL21, CFD, and ACKR1) in endometriosis were identified, which were able to accurately predict the occurrence of endometriosis. The expression of CCL21 was obviously increased in the EcE of endometriosis patients and mouse models. Knockdown of CCL21 inhibited the proliferation, migration, and invasion of 12z cells and promoted apoptosis. Mechanistically, reduced CCL21 alleviated the pathology of endometriosis through restraining the activation of the NF-κB signaling pathway and the downstream inflammatory factors (IL-6, IL-1β, and TNF-α). In conclusion, increased CCL21 promoted the development of endometriosis by activating the NF-κB signaling pathway, and this finding offers a novel therapeutic target for treatment.