Endostatin's antiangiogenic signaling network
Endostatin's antiangiogenic signaling network
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DOI：
10.1016/s1097-2765(04)00102-9
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发表时间：
2004-03-12
期刊：
影响因子：
16
通讯作者：
Huber, PE
中科院分区：
文献类型：
--
作者：
Abdollahi, A;Hahnfeldt, P;Huber, PE
这表明，组织中血管生成平衡的一组基因表达可以通过单个蛋白质在分子上集体重置。利用全基因组表达谱，结合RT-PCR和磷酸化分析，我们发现内源性血管生成抑制剂内皮抑素下调了人微血管内皮中与促血管生成活性相关的许多信号通路。同时，内皮抑素被发现上调许多抗血管生成基因。结果是基因调控方向和血管生成状态之间的独特对齐。分析进一步揭示了迄今为止与血管生成无关的基因调控。我们对共调控基因的分析表明，在一个复杂的信号网络中，复杂的通路间通信既概括又扩展了当前对血管生成过程的理解。更一般地说，从细胞生物学和治疗的角度揭示了遗传网络的本质。
It is here demonstrated that the set of gene expressions underlying the angiogenic balance in tissues can be molecularly reset en masse by a single protein. Using genome-wide expression profiling, coupled with RT-PCR and phosphorylation analysis, we show that the endogenous angiogenesis inhibitor endostatin down-regulates many signaling pathways in human microvascular endothelium associated with proangiogenic activity. Simultaneously, endostatin is found to upregulate many antiangiogenic genes. The result is a unique alignment between the direction of gene regulation and angiogenic status. Profiling further reveals the regulation of genes not heretofore associated with angiogenesis. Our analysis of coregulated genes shows complex interpathway communications in an intricate signaling network that both recapitulates and extends on current understanding of the angiogenic process. More generally, insights into the nature of genetic networking from the cell biologic and therapeutic perspectives are revealed.