A role for Hox A5 in regulating angiogenesis and vascular Patterning
A role for Hox A5 in regulating angiogenesis and vascular Patterning
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DOI：
10.1089/lrb.2005.3.240
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发表时间：
2005-01-01
影响因子：
1.4
通讯作者：
Boudreau, Nancy
中科院分区：
文献类型：
--
作者：
Rhoads, Kim;Arderiu, Gemma;Boudreau, Nancy
背景资料：同源异型盒（Homeobox，Hox）基因是一种转录调控因子，通过调控与细胞-细胞或细胞外基质（ECM）相互作用相关的基因来调节胚胎形态发生和成人病理组织重塑。我们以前表明，虽然Hox 3基因促进血管生成，Hox D10抑制这一进程。方法和结果：在这里，我们表明，另一个Hox家族基因，Hox AS，也阻止血管生成，但通过靶向不同的下游基因比Hox D10来实现这一点。Hox AS的持续表达导致许多促血管生成基因的下调，包括VEGF 2、肝配蛋白A1、Hif 1 α和考克斯-2。此外，Hox AS还上调抗血管生成基因（包括血小板反应蛋白-2）的表达。此外，我们发现，虽然Hox AS mRNA在静止的内皮细胞（EC）中表达，但在与乳腺肿瘤相关的活跃的血管生成EC或增殖的婴儿血管瘤中，其表达减少或缺失。结论：我们的研究结果表明，恢复Hox A5表达可能提供一种新的手段来限制乳腺肿瘤生长或血管瘤扩张
Background: Homeobox (Hox) genes are transcriptional regulators which modulate embryonic morphogenesis and pathological tissue remodeling in adults via regulation of genes associated with cell-cell or cell extracellular matrix (ECM) interactions. We previously showed that while Hox 3 genes promote angiogenesis, Hox D10 inhibits this process.Methods and Results: Here we show that another Hox family gene, Hox AS, also blocks angiogenesis but accomplishes this by targeting different downstream genes than Hox D10. Sustained expression of Hox AS leads to down regulation of many pro-angiogenic genes including VEGFR2, ephrin A1, Hif1 alpha and COX-2. In addition, Hox AS also upregulates expression of anti-angiogenic genes including Thrombospondin-2. Furthermore, we show that while Hox AS mRNA is expressed in quiescent endothelial cells (EC), its expression is diminished or absent in active angiogenic EC found in association with breast tumors or in proliferating infantile hemangiomas.Conclusions: Together our results suggest that restoring Hox A5 expression may provide a novel means to limit breast tumor growth or expansion of hemangiomas