アクティブボード・2017年4月
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研究発表を行った学会;
   19th International Vascular Biology Meeting
   2016年10月30日〜11月3日(Boston, USA)
タイトル;Endothelial cell specific-and organ specific-early growth response-3 promoter activation revealed diverse patterns in developmental and postnatal vascular remodeling stages.
発表者;村松 昌 氏
   (熊本大学 生命資源研究・支援センター 表現型解析分野)
要旨;
Endothelial cells (EC) constantly senses and responds to changes in microenvironment, primarily at the epigenetic transcription level. We previously reported that Early Growth Response (EGR)-3 predominantly regulated EC proliferations, migrations, and tube formations in primary cultured ECs (Blood, 2010). Here, to characterize the role of egr-3 expression in vivo, a 2.5 kbp of Egr-3 promoter was coupled to lacZ, which was knocked into hprt-locus of mice. Generated the Egr-3 promoter-lacZ hprt mice revealed uniform and specific activations into the endothelium. In parallel comparison to tie2 promoter-lacZ hprt mice, Egr-3 promoter activities were much higher than the tie2 in most organs except lung and kidney. Compared to an EC-specific promoter activity in postnatal period, unexpectedly, such activity was completely absent in embryo until E16. After the period, EC-specific promoter activations were occurred in whole embryos but not vitelline vessels. Those phenomena were sharp contrast to the EC-specific tie2 promoter activities in embryo. Microarrays and protein profiling analysis from dermal mRNAs and proteins between E14 and E16, revealed that both tissue factor (TF) mRNA and the protein were markedly increased in E16. TF is known to not only thrombosis initiation factor in pathology, but also vascular remodeling factor in developmental stage. Taken together with angiogenic initiator functions of EGR3, these findings suggest that there are additional vascular remodeling (activation) phase in around E16, after the hemangioblast differentiation. Further experiments with TF-mediated functions would uncover the mechanism to understand the vascular-bed specific regulations in developmental stage.