Mutual Balance between Vasohibin-1 and Soluble VEGFR-1 in Endothelial Cells
Mutual Balance between Vasohibin-1 and Soluble VEGFR-1 in Endothelial Cells
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DOI：
10.3390/ph4060782
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发表时间：
2011-06-01
期刊：
影响因子：
4.6
通讯作者：
Sato, Yasufumi
中科院分区：
文献类型：
--
作者：
Miyashita, Hiroki;Suzuki, Hirotada;Sato, Yasufumi
Vasohibin-1（VASH 1）是内皮细胞（EC）的VEGF诱导基因，其作为血管生成的负反馈调节剂起作用。为了进一步研究VASH 1的功能，我们将人VASH 1基因转染到小鼠EC系MS 1中，建立了稳定表达VASH 1的克隆，并通过cDNA微阵列分析来确定基因的改变。在各种血管生成相关基因中，血管内皮生长因子1型受体（VEGFR-1）及其可变剪接形式可溶性VEGFR-1（sVEGFR-1）被发现是最显著下调的基因。VASH 1在人脐静脉内皮细胞中的瞬时过表达证实了VEGFR-1和sVEGFR-1的下调。sVEGFR-1是VEGF的诱饵受体并抑制血管生成。有趣的是，当sVEGFR-1在EC中过表达时，它反过来抑制VASH 1的表达。这些结果表明，VASH 1和sVEGFR-1，两种血管生成抑制剂，相互平衡它们在EC中的表达。
Vasohibin-1 (VASH1) is a VEGF-inducible gene of endothelial cells (ECs) that acts as a negative feedback regulator of angiogenesis. To further characterize the function of VASH1, we transfected human VASH1 gene into the mouse EC line MS1, established stable VASH1 expressing clones, and determined gene alteration by cDNA microarray analysis. Among the various angiogenesis-related genes, vascular endothelial growth factor type 1 receptor (VEGFR-1) and its alternative spliced form, soluble VEGFR1 (sVEGFR-1), were found to be the most significantly down-regulated genes. Transient overexpression of VASH1 in human umbilical vein endothelial cells confirmed the down-regulation of VEGFR-1 and sVEGFR-1. sVEGFR-1 is a decoy receptor for VEGF and inhibits angiogenesis. Interestingly, when sVEGFR-1 was overexpressed in ECs, it inhibited the expression of VASH1 in turn. These results suggest that VASH1 and sVEGFR-1, two angiogenesis inhibitors, mutually balance their expressions in ECs.