血管通透性對於在許多器官而言，是種複雜的調控機制，在血管新生、腫瘤轉移和發炎反應等，都會引發血管通透性，然而這些生理病變的發生，往往伴隨著Egr-1的活化。Egr-1是屬於立即調控基因家族的成員之一，為一個鋅手指的轉錄因子，在血管受到傷害、生長因子、細胞激素、賀爾蒙以及環境的影響下，Egr-1的表現量會上升。一但Egr-1被誘導後，Egr-1會和coactivators或者corepressor結合在標的基因啟動子的GC序列上，調控其轉錄的活性。Cav-1在內皮細胞中，被大量的表現，調控著物質間的運輸、滲透性的影響和血管新生。利用生物資訊工具，在Cav-1的啟動子上面，發現有Egr-1的結合位，我們因此假設，Egr-1可能具有調控Cav-1轉錄的活性，進而去影響血管的通透性，在我們的研究發現中，內生性Egr-1缺陷的內皮細胞中，VEGF-A不能誘導其通透性的增加。在啟動子的報告基因的證明下，Egr-1可以單獨促進Cav-1啟動子的活性；但在NAB2存在下，Egr-1可抑制Cav-1啟動子的活性。同時在內皮細胞中，Egr-1表現會增加NAB2的表現，進而降低Cav-1 mRNA和蛋白質的表現。綜合以上結果，Egr-1經由NAB2的影響，而為Cav-1負調控者，因此，Egr-1在血管通透性調節上扮演重要的角色。

Vascular permeability is a tightly regulated process in various organ beds and an essential component of angiogenesis, tumor metastasis, and inflammation. Early growth response-1 gene (EGR-1) is a member of immediate-early gene family. Egr-1 encodes a zinc finger-containing DNA-binding protein and is up-regulated by mechanical injury, numerous agonists such as growth factors, cytokines, hormones and environmental stimuli. Once induction, Egr-1 together with coactivators or corepressors binds to GC consensus sequences in the promoter region of target genes, resulting in transcriptional activation or repression. We have previously shown that Egr-1 deficient mice lost the ability to respond to VEGF-A-induced vessel permeability. Caveolin 1 (Cav-1) is an abundant protein in endothelial cells (ECs), which regulate transcytosis, permeability, vascular tone, and angiogenesis. By using bioinformatic tools, we found several putative Egr-1 binding sites in the Cav-1 promoter. We hypothesized that Egr-1 might be a transcription mediator for the expression of Cav-1. In our study, ECs lack of endogenous Egr-1 in vitro lost the ability to respond to VEGF-mediated increase of vascular permeability, suggesting a role of Egr-1 in vascular permeability. Promoter-driven luciferase assay was used to show that Egr-1 alone promoted Cav-1 promoter activity. Egr-1 together with NAB2, a corepressor of Egr-1, inhibited the Cav-1 promoter activity. Consistent with the notion, Egr-1 overexpression increased NAB2 expression while decreasing Cav-1 expression at mRNA and protein levels. Together, Egr-1 negatively mediated Cav-1 expression partly via induction of NAB2.Egr-1 thus is a novel mediator for vascular permeability.

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