Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Exp Cell Res. 2013 Mar 10;319(5):707-17. doi: 10.1016/j.yexcr.2013.01.004. Epub 2013 Jan 16.
Angiogenesis is a vital process for proper embryonic development, wound healing, malignant tumor growth and metastasis. Two glia maturation factor genes, glia maturation factor-β (GMFB) and glia maturation factor-γ (GMFG), presenting different expression patterns and distinct biological functions are found in vertebrates. But, the role of GMFB and GMFG in vascular development remains largely unknown. Here, we showed that both GMFB and GMFG are highly conserved in vertebrates. Whole-mount in situ hybridization and quantitative RT-PCR results revealed that GMFB and GMFG were differently expressed during zebrafish embryogenesis. GMFB was highly enriched in brain and GMFG was predominantly expressed in endothelial cells. By gene specific MO, knockdown of GMFG, but not GMFB, severely disrupted angiogenic sprouting of intersegmental vessels (ISVs), but this angiogenic defects were prevented by overexpression of a MO-resistant form of zebrafish GMFG mRNA. In addition, the expressions of angiogenic factors VEGF-A, STAT3, MMP2, MMP9, and MMP13 were significantly decreased in endothelial cells of GMFG morphants. Our findings provide the first in vivo evidence that GMFG is an important regulator for angiogenic sprouting during angiogenesis in zebrafish and suggest that GMFG may act as a novel potential target for anti-angiogenesis therapy in clinical settings.
血管生成对于胚胎正常发育、创伤愈合、恶性肿瘤生长和转移都是至关重要的过程。两种神经胶质细胞成熟因子基因，神经胶质细胞成熟因子-β（GMFB）和神经胶质细胞成熟因子-γ（GMFG），在脊椎动物中表现出不同的表达模式和不同的生物学功能。但是，GMFB 和 GMFG 在血管发育中的作用在很大程度上仍然未知。在这里，我们表明 GMFB 和 GMFG 在脊椎动物中高度保守。整体原位杂交和定量 RT-PCR 结果表明，GMFB 和 GMFG 在斑马鱼胚胎发生过程中呈现不同的表达。GMFB 在大脑中高度富集，而 GMFG 主要在血管内皮细胞中表达。通过基因特异性 MO，GMFG 的敲低，而不是 GMFB 的敲低，严重破坏了节间血管（ISVs）的血管生成发芽，但通过过表达一种 MO 抗性形式的斑马鱼 GMFG mRNA 可以预防这种血管生成缺陷。此外，GMFG 形态发生体中血管生成因子 VEGF-A、STAT3、MMP2、MMP9 和 MMP13 的表达显著降低。我们的研究结果提供了 GMFG 是斑马鱼血管生成中血管生成发芽的重要调节因子的第一个体内证据，并表明 GMFG 可能作为临床抗血管生成治疗的新的潜在靶点。
