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

Endometriosis, affecting approximately 10% of reproductive-aged women worldwide, is widely recognized as a chronic inflammatory disease. Inflammation-related genes (IRGs) play a crucial role in the occurrence and progression of various diseases, including endometriosis. However, identifying the key IRGs that drive endometriosis pathologyand whether they can be therapeutically targeted remains unclear. 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 significantly increased in the EcE in EcE from patients with endometriosis and in endometriosis-like lesions from mice. Knockdown of CCL21 inhibited the proliferation, migration, and invasion of 12z cells and promoted apoptosis. Mechanistically, CCL21 knockdown attenuated endometriosis-associated inflammatory signaling 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 regulating inflammatory cytokine and activating the NF-κB signaling pathway. This finding offers a novel therapeutic target for treatment.