维生素D结合蛋白抑制VEGF信号通路参与子痫前期发病相关机制

The role of vitamin D binding protein (DBP) in tumor angiogenesis has been subject to attention in recent years, but the mechanism of DBP inhibiting of VEGF signaling pathway specific is unknown, and research of DBP in preeclampsia have not been valued. Our previous studies showed that the expression of DBP in preeclampsia placenta is inversely proportional to placental microvascular density and DBP is secretied by trophoblast cells. In order to explain this phenomenon, we hypothesize that DBP anti-placental angiogenesis by inhibiting VEGF signaling pathways and may lead to the onset of preeclampsia. DBP may affect VEGF synthesis or inhibit VEGFR-2 phosphorylation to regulate VEGF signaling pathways. To test this hypothesis, we intend to use the primary trophoblast cells and vascular endothelial cells co-cultured, transfected plasmid aspects depth and Western Blot, from the level of molecules, proteins and cells to clear antiangiogenic mechanism of DBP. The study will provide new idea of anti-placental angiogenesis and more information for the etiology of Preeclampsia.

维生素D结合蛋白（DBP）在肿瘤血管生成的作用近年来受到关注，但DBP抑制VEGF信号通路的具体机制不明，且目前子痫前期胎盘中DBP的研究尚未受重视。我们前期发现子痫前期中DBP高表达，而胎盘微血管密度降低；DBP定位于胎盘合体滋养细胞，并由滋养细胞分泌。为解释此现象，我们提出假说，滋养细胞分泌的DBP作用于血管内皮细胞，通过维生素D代谢途径影响VEGF合成或直接抑制VEGFR-2磷酸化调控VEGF及其下游信号通路抗胎盘血管生成。为验证这一假说，我们拟采用原代滋养细胞与血管内皮细胞共培养、质粒转染、Western Blot等手段，从分子、蛋白及细胞水平多方面深入探讨DBP抗血管生成的相关机制，明确其与VEGF信号通路之间的关系。本研究将从DBP这一全新角度补充现有的胎盘血管形成不良病因，为子痫前期的发病机制研究提供新思路。