Conclusions
Thus, we demonstrated that NCOA6 is important for cytotrophoblast invasion/migration, at least partially, by activating NF-κB-mediated MMP9 transcription; the downregulation of NCOA6 may contribute to the pathogenesis of early-onset sPE.
Methods
Human placenta tissues were collected from normal pregnancies and pregnancies complicated by early-onset severe preeclampsia (sPE). Immunofluorescence, RT-qPCR and Western blotting were used to determine NCOA6 expression. Transwell invasion/migration assays were performed to explore whether NCOA6 knockdown affected human placenta-derived HTR-8/SVneo cell invasion/migration. Gelatin zymography was performed to examine the change in the gelatinolytic activities of secreted MMP2 and MMP9. Luciferase reporter assays were used to explore whether NCOA6 coactivated NF-κB-mediated MMP9 transcription.
Results
NCOA6 is mainly expressed in the human placental trophoblast column, as well as in the EVTs. HTR-8/SVneo cell invasion and migration were significantly attenuated after NCOA6 knockdown, and the secretion of MMP9 was decreased due to transcriptional suppression. NCOA6 was further found to coactivate NF-κB-mediated MMP9 transcription. Moreover, expression of NCOA6 was impaired in placentas of patients complicated by early-onset sPE. Conclusions: Thus, we demonstrated that NCOA6 is important for cytotrophoblast invasion/migration, at least partially, by activating NF-κB-mediated MMP9 transcription; the downregulation of NCOA6 may contribute to the pathogenesis of early-onset sPE.