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

Shh 和 FGF-2 对 angiopoietin-1 和 angiopoietin-2 表达平衡的调节：Shh 在血管生成中的作用。

• 批准号: 23591890
• 负责人: FUJII TAKAAKI
• 金额: $ 3.41万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591890/
• 关键词: Shh; FGF-2; 血管新生; VEGF; 糖尿病; shh; angiopoietin; リンパ節転移

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.

Sonic hedgehog（Shh）是一种间接的血管生成剂，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，由Shh诱导的血管生成的特征在于具有较少分支的明显大直径血管。Ang-1促进血管成熟，血管生成素-2（Ang-2）抵消Ang-1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，并且我们研究了Shh在体外对血管生成素的调节系统。Shh增强成纤维细胞中Ang-1的表达，但不增强VEGF。成纤维细胞生长因子-2（FGF-2）（一种有效的血管生成因子）显著降低了Shh对Ang-1表达的上调。此外，FGF-2可增加血管内皮细胞中Ang-2的表达。这些结果表明，Shh和FGF-2调节血管形态发生素Ang-1和Ang-2的表达平衡，并参与血管生成。