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)是一种间接血管生成剂，可上调其他血管生成因子，包括血管生成素-1(Ang-1)。最近的研究表明，Shh诱导的血管生成的特点是明显的大直径血管，分支较少。血管生成素-1(Ang-1)促进血管成熟，血管生成素-2(Ang-2)拮抗Ang-1活性，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可促进成纤维细胞中Ang-1的表达，但不能促进成纤维细胞中血管内皮生长因子的表达。成纤维细胞生长因子-2(成纤维细胞生长因子-2)可显著抑制Shh对Ang-1表达的上调。此外，成纤维细胞生长因子-2增加血管内皮细胞Ang-2的表达。这些结果提示Shh和FGF-2调节血管形成因子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.