VEGF deprivation affects endoglin expression in trophoblast cells and natural killers

Vascular Endothelial Growth Factors (VEGFs) are a group of proteins involved in differentiation of various cell types including endothelial cells, monocytes, macrophages, stem cells, tumor cells, vascular smooth muscle cells, trophoblast cells, and other cell populations that express VEGF receptors. Pathological conditions, such as abnormalities in placental development, can be caused by altered production and signaling of VEGFs. Trophoblast cells play a significant role in placental formation and are essential for angiogenesis due to their secretion and reception of VEGF. However, there is a lack of information in the literature regarding the influence of VEGF on functional characteristics of trophoblast cells. Maternal immune cells, particularly natural killer (NK) cells, have been shown to affect the activity of trophoblasts during pregnancy. Given the high abundance of NK cells in decidual tissue, it is important to evaluate their potential influence on phenotype of trophoblast cells. In this study, we investigated the expression of MICA, MICB, and CD105 proteins by NK cells and trophoblast cells. MICA and MICB are stress markers that allow us to assess cell viability. CD105 is a receptor expressed on the surface of various cell types. It plays a role in signal transmission from TGF-β family proteins. In particular, endoglin has been shown to regulate signaling from TGF-β by directing signals through the SMAD2/3 or SMAD1/5/8 pathways. According to the literature, endoglin inhibits the SMAD3- mediated signaling. However, similar effects of endoglin have not been confirmed for NK cells and trophoblasts. The studies of endoglin expression levels are of importance, since the signals from TGF-β are essential for differentiation of trophoblast cells. Disruption of TGF-β signaling can lead to pregnancy complications and miscarriage. We have demonstrated that VEGF plays a role in regulating the activity of trophoblasts and NK cells. In particular, treatment with neutralizing monoclonal antibodies to VEGF-A was associated with reduced expression of CD105, a VEGF coreceptor, on trophoblasts and NK cells under co-culture conditions. However, pretreatment of trophoblasts with anti-VEGF antibodies did not alter their resistance to the cytotoxic activity of NK cells. Taken together, these findings suggest that inhibition of VEGF signaling results in significant changes in reception of TGF-β family proteins by trophoblasts and natural killer cells.