TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta

Abstract

Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.