The activation of TGF-β signaling promotes cell migration and invasion of ectopic endometrium by targeting NRP2.

Endometriosis is a gynecological disorder seriously affecting the health and life of women of reproductive age. Neuropilin 2 (NRP2) has been indicated to display a high level in ectopic endometrium. Nevertheless, the specific function of NRP2 in endometriosis is unanswered. RT-qPCR was utilized to detect expression of NRP2 and SMAD family member 2 (SMAD2) in endometrial tissues or endometrial stromal cells (ESCs). Protein levels of transforming growth factor beta (TGF-β) signaling-associated markers and epithelial-mesenchymal transition (EMT)-related markers were examined by western blotting. Transwell assays were utilized for detecting the impact of NRP2 on ectopic ESC phenotypes. ChIP and luciferase reporter assays were performed for identification of the relationship between NRP2 and SMAD2. In this study, NRP2 was overexpressed in ectopic endometria in comparison to eutopic endometria. Depletion of NRP2 restrained ectopic ESC migration, invasiveness and EMT. TGF-β signaling-mediated activation of SMAD2 transcriptionally upregulated NRP2 expression in ectopic ESCs. TGF-β treatment could rescue NRP2 silencing-induced suppressive impact on the behaviors of ectopic ESCs. Overall, the activation of TGF-β signaling contributes to the migration and invasiveness of ectopic ESCs by targeting NRP2.