| Co-Investigator(Kenkyū-buntansha) |
MITSUI Yoji National Institute of Bioscience and Human-Technology, the chief investigator, 主席研究官
NISHIKAWA Shin-ichi Kyoto University, Professor, 大学院・医学研究科, 教授 (60127115)
SHIBUYA Masabumi University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107427)
FUJIWARA Keigi National Cardiovascular Center Research Institute, the chief investigator, 循環器形態部長 (10190092)
TSUKITA Shoichirou Kyoto University, Professor, 大学院・医学研究科, 教授 (50155347)
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| Research Abstract |
(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.
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