Molecular mechanism of vascular formation

(1)转录因子Ets1的瞬时过表达促进内皮细胞的凋亡。Ets1使促凋亡的Bid、细胞色素P450、caspase-4、p27和p21的表达增加2倍以上，而使抗凋亡的DAD-1、Ax1、COX-2、IAP-2和MDM-2的表达降低不到0。在ECS中有5倍。(2)大血管内皮细胞和小血管内皮细胞的血管内皮生长因子信号转导途径不同。尤其是RAS在小血管内皮细胞中起重要作用。(3)转基因小鼠实验表明，血管内皮生长因子-E作为血管内皮生长因子家族的新成员，在未发现血管通透性的情况下，可促进血管生成。(4)VEGFR-2(KDR)的自磷酸化位点为1175Y和1214Y。γ的羧基末端SH2结构域与磷酸化的1214Y结合，是激活MAPK和增强DNA合成所必需的。(5)MadCAM-1在胚胎早期静脉内皮细胞中特异表达。BMP-4可增加MadCAM-1阳性静脉内皮细胞的数量。(6)将GFP标记基因稳定导入小鼠胚胎干细胞。建立时间-RAP视频系统，分析ES细胞的分化和GFP标记基因的表达模式。(7)确定了对claudin-5和EC特异性claudin的靶向销毁。(8)将人TERT基因和SV40T抗原基因导入人脐静脉内皮细胞。该转染表显示了细胞分裂能力的延长，并被建议产生一种新的自分泌生长因子。

(1) Transient overexpression of transcription factor Ets1 promoted apoptosis of endothelial cells (Ecs). Ets1 increased expression of pro-apoptotic Bid, cytochrome p450, caspase-4, p27 and p21 more than 2 fold, while it decreased expression of anti-apoptotic DAD-1, AXL, Cox-2, IAP-2, and MDM-2 less than 0. 5 fold in Ecs. (2) The signal transduction pathway of VEGF appeared to be different between ECs of large vessels and small vessels. Especially, Ras played an important role in ECs of small vessels. (3) Transgenic mouse experiment revealed that VEGF-E, a new member of VEGF family, promoted angiogenesis without any evidences of vascular permeability. (4) Autophosphorylation sites of VEGFR-2 (KDR) were determined to be 1175Y and 1214Y. Carboxyl-terminal SH2 domain of PLC-γ bound to phosphorylated 1214Y, which was indispensable for the MAPK activation and augmented DNA synthesis. (5) MadCAM-1 was specifically expressed in venous ECs in the early embryonic stage. BMP-4 increased the number of MadCAM-1 positive venous ECs. (6) GFP-tagged genes were stably introduced into mouse embryonic stem (ES) cells. Time-rap video system was established to analyze the differentiation of ES cells and the expression pattern of GFP-tagged genes. (7) Target destruction of claudin-5, and EC-specific claudin, was established. (8) Human TERT gene and SV40 T antigen gene were introduced into human umbilical vein ECs (HUVECS). The table transfectants exhibited the prolongation of cell-division capability and were suggested to produce a novel autocrine growth factor.