Transcriptional Factor Forkhead Box D1 Upregulates Sirtuin3 by Activating the Wnt/β-Catenin Pathway to Alleviate HTR-8/Svneo Trophoblast Cell Dysfunction in Preeclampsia

Abstract

The proliferation, invasion, migration and apoptosis of trophoblast cells in preeclampsia are closely related to the occurrence and development of preeclampsia. Transcription factors forkhead box D1 and Sirtuin3 are abnormally expressed in preeclampsia, and Sirtuin3 plays a regulatory role in cell proliferation, invasion and apoptosis in related diseases. However, the studies on forkhead box D1 and Sirtuin3 in preeclampsia and their specific mechanisms have not been reported so far. In this study, the expression of Sirtuin3 in Human chorionic trophoblast cells HTR-8/Svneo was inhibited by cell transfection, and then the effects of Sirtuin3 expression in interfering cells on cell invasion, migration and apoptosis were detected by MTT, TUNEL, Western blot, wound healing and Transwell techniques. Subsequently, the binding between forkhead box D1 and Sirtuin3 was predicted by JASPAR website and verified by luciferase assay and ChIP assay. Finally, cell invasion, migration and apoptosis were detected after overexpression of forkhead box D1 and interference with Sirtuin3, and the Wnt/β-catenin signaling pathway was detected to explore the mechanism. We found that interfering with Sirtuin3 induced apoptosis of HTR-8/Svneo cells and inhibited cell invasion and migration. Forkhead box D1 transcriptional activation of Sirtuin3 alleviated HTR-8/SVneo cell dysfunction through activation of the Wnt/β-catenin signaling pathway. Overall, transcriptional factor forkhead box D1 can upregulate Sirtuin3 by activating the Wnt/β-catenin pathway to alleviate HTR-8/Svneo trophoblast cell dysfunction in preeclampsia.