VEGF DEPRIVATION AFFECTS ENDOGLIN EXPRESSION IN TROPHOBLAST CELLS AND NATURAL KILLERS

Vascular Endothelial Growth Factors (VEGFs) are a group of proteins that involved in the development of various cell types, including endothelial cells, monocytes, macrophages, stem cells, tumor cells, vascular smooth muscle cells, trophoblast cells, and other cells that express VEGF receptors.  Pathological conditions, such as abnormalities in placental development, can be caused by disruptions in the 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 signaling in trophoblast cells on their functional characteristics. 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 the decidual tissue, it is important to consider their potential influence on the phenotypic changes in 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 that is expressed on the surface of various cell types and plays a role in signal transmission from TGFβ family proteins. In particular, endoglin has been shown to regulate signaling from TGFβ by directing signals through the SMAD2/3 or SMAD1/5/8 pathways. According to the literature, endoglin inhibits signaling involving SMAD3. However, it has not yet been determined whether endoglin plays a similar role in NK cells and trophoblasts. The investigation of changes in endoglin expression is a significant issue, as signals from TGFβ are essential for the differentiation of trophoblast cells. Disruption of TGFβ 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 resulted in inhibition of the 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 the reception of TGFβ family proteins by trophoblasts and natural killer cells.

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