アクティブボード・2016年3月
     ・・・・・2016年 3月 1日更新・・・・・
研究発表を行った学会;
・International Vascular Biology Meeting 2014
 2014年4月14日〜17日(京都市)
タイトル;Pro-angiogenic signal mediator-early growth response 3 promoter direct vascular bed-specific gene expression in adult mice.
発表者;槙原  千嘉 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 cell activation and dysfunction underlie many vascular diseases including atherosclerosis, thrombosis, and pathological angiogenesis. Endothelial cell activation is mediated primarily at the level of gene transcription. We previously reported that several activation agonists such as VEGF, TNF-α, and thrombin, rapidly and profoundly induced the early growth response (Egr)-3 genes in primary cultured endothelial cells. Knockdown of Egr-3 markedly impaired VEGF-mediated tube formation, vascular outgrowth from ex vivo aortic rings, and melanoma tumor growth in vivo (Blood, 2010). In order to characterize the role of the promoter that drives egr-3 expression in mediating inducible expression in vivo, we studied on a DNA construct containing 2.5 kb of human Egr-3 promoter coupled to lacZ reporter, which is inserted in hypoxanthine guanine phosphoribosyltransferase (Hprt) locus of mice. Compared to 0.8 kb of tie2 promoter knocked into the same locus which is the predominantly endothelial specific, Egr-3 promoter-mediated lacZ was uniformly and specifically expressed in the endothelium of transgenic many adult organs except kidney. It was, however, not highly expressed in developmental embryos. Systemic administration of VEGF or LPS in adult mice resulted in the activation of Egr-3 promoter and endogenous gene expression in subset of organs including brain and heart. Moreover, Egr-3 locus obtained unique histone modifications after the VEGF stimulus on our global histone ChIP-seq mappings. Taken together, these findings suggest that 2.5 kb Egr-3 promoter directs vascular bed-specific expression in activated adult endothelium and Egr-3 works for the critical transcription factor mediating the pro-angiogenic signaling.