Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh D A
Department of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Cell Biol. 1997 Oct 6;139(1):257-64. doi: 10.1083/jcb.139.1.257.
Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin alphavbeta3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin alphavbeta3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin alphavbeta3 and uPA. In fact, sustained expression of Hox D3 in vivo on the chick chorioallantoic membrane retained EC in this invasive state and prevented vessel maturation leading to vascular malformations and endotheliomas. Therefore, Hox D3 regulates EC gene expression associated with the invasive stage of angiogenesis.
血管生成的特征是血管内皮细胞（EC）出现明显的表型变化。有证据表明，Hox D3同源框基因介导内皮细胞从静止状态转变为血管生成/侵袭状态。用碱性成纤维细胞生长因子（bFGF）刺激内皮细胞会导致Hox D3、整合素αvβ3和尿激酶型纤溶酶原激活剂（uPA）的表达增加。Hox D3反义寡核苷酸阻断了bFGF诱导uPA和整合素αvβ3表达的能力，但对内皮细胞增殖或bFGF介导的细胞周期蛋白D1表达没有影响。在没有bFGF的情况下，Hox D3的表达导致整合素αvβ3和uPA的表达增强。事实上，在鸡胚绒毛尿囊膜上体内持续表达Hox D3会使内皮细胞保持在这种侵袭状态，并阻止血管成熟，导致血管畸形和内皮瘤。因此，Hox D3调节与血管生成侵袭阶段相关的内皮细胞基因表达。
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