Reduced FOXM1 Expression Limits Trophoblast Migration and Angiogenesis and Is Associated With Preeclampsia
Abstract
Trophoblast cells are often compared to highly invasive carcinoma cells due to their capacity to proliferate in hypoxic conditions and to exhibit analogous vascular, proliferative, migratory, and invasive capacities. Thus, genes that are important for tumorigenesis, such as forkhead box M1 ( FOXM1) may also be involved in processes of trophoblast invasion. Indeed, we found Foxm1 protein and messenger RNA (mRNA) levels decreased as gestational age increased in rat's placentae. Accordingly, when mimicking early placental events in vitro, protein and mRNA expression of FOXM1 increased from 21% to 8% O2, reaching its highest expression at 3% oxygen tension, which reflects early implantation environment, and dropping to very low levels at 1% O2. Remarkably, FOXM1 silencing in JEG-3 cells was able to significantly decrease migration by 27.9%, in comparison with those cells transfected with control siRNA. Moreover, angiogenesis was compromised when conditioned media (CM) from FOXM1-siRNA -JEG-3 (3% O2) was added to human umbilical vein endothelial cells (HUVEC) cells; however, when CM of JEG-3 cells overexpressing FOXM1 at 1% O2 was added, the ability of HUVEC to form tubule networks was restored. Additionally, quantitative real-time ...Continue Reading
References
Autophagy induced by HIF1α overexpression supports trophoblast invasion by supplying cellular energy
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