Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2: The role of Shh in angiogenesis.

Sonic hedgehog （Shh）是一种间接的血管生成因子，可上调其他血管生成因子，包括血管生成素-1 （ang1）。最近的研究表明，Shh诱导的血管生成以明显的大直径血管和较少的分支为特征。Ang-1促进血管成熟，血管生成素-2 （ang2）抵消Ang-1的活性并调节血管分支。因此，我们假设Shh诱导的血管生成受Ang-1和Ang-2表达的影响，并在体外研究了Shh对血管生成素的调控系统。Shh增强了成纤维细胞中Ang-1的表达，但没有增强VEGF。成纤维细胞生长因子-2 （FGF-2）可显著降低Shh对Ang-1表达的上调。此外，FGF-2增加内皮细胞中Ang-2的表达。这些发现提示Shh和FGF-2调节血管形态因子Ang-1和Ang-2的表达平衡，参与血管生成。

Sonic hedgehog (Shh) is an indirect angiogenic agent upregulating other angiogenic factors, including angiopoietin-1 (Ang-1). Recent studies revealed that angiogenesis induced by Shh is characterized by distinct large-diameter vessels with less branching. Ang-1 promotes blood vessel maturation, and angiopoietin-2 (Ang-2) counteracts Ang-1 activity and regulates vascular branching. Thus we hypothesized that Shh-induced angiogenesis is affected by expression of Ang-1 and Ang-2, and we investigated the regulatory system of angiopoietins by Shh in vitro. Shh enhanced Ang-1 expression, but did not enhance VEGF in fibroblasts. The upregulation of Ang-1 expression by Shh was significantly decreased by fibroblast growth factor-2 (FGF-2), a potent angiogenic factor. Furthermore, FGF-2 increased the expression of Ang-2 in endothelial cells. These findings suggest that Shh and FGF-2 regulate the expression balance of vascular morphogens Ang-1 and Ang-2 and are involved in angiogenesis.