FrzA, a secreted frizzled related protein, induced angiogenic response
FrzA, a secreted frizzled related protein, induced angiogenic response
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DOI：
10.1161/01.cir.0000039342.85015.5c
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发表时间：
2002-12-10
期刊：
影响因子：
37.8
通讯作者：
Duplàa, C
中科院分区：
文献类型：
--
作者：
Dufourcq, P;Couffinhal, T;Duplàa, C
背景-分泌的卷曲相关蛋白(SFRP)是被认为干扰WRIT信号的可溶性蛋白质。我们的研究小组先前证明了其中一个成员SFRP-1/FrzA在胚胎血管形成过程的早期阶段以及在成人的动脉和毛细血管内皮细胞中强烈表达，并调节血管细胞的增殖。方法和结果-对SFRP-1在周期卵巢血管生成过程中的表达分析表明，SFRP-1在新生血管形成过程中表达，当血管形成完全成熟时检测不到。然后我们研究了FrzA在几种不同的血管生成模型中的作用。FrzA诱导鸡绒毛膜尿囊膜模型血管生成。此外，AdFrzA基因在移植的间充质细胞和胶质瘤细胞中的转移增加了血管密度和肿瘤生长。FrzA诱导了血管的形成，与对照相比，这些血管更大、更长、更成熟。在体外，FrzA促进内皮细胞的迁移和管状形成，并似乎保护它们免受凋亡。FrzA在体外的血管生成作用不依赖于血管内皮生长因子、成纤维细胞生长因子-2或Angiopiotin-1的诱导和Akt的激活。结论：这些结果表明FrzA具有促血管生成作用，提示WRIT信号可能参与了正常分化和血管系统的病理发展。
Background-The secreted frizzled related proteins (sFRP) are soluble proteins thought to interfere with the Writ signaling. Our group previously demonstrated that one of these members, sFRP-1/FrzA, is strongly expressed during early phases of the vascularization process in embryonic vasculature and in the endothelium of arteries and capillaries in adults and modulated vascular cell proliferation.Methods and Results-Analysis of the expression of sFRP-1 during cyclic ovarian angiogenesis revealed that sFRP-1 is expressed during the formation of neovessels and becomes undetectable when the vasculature is fully maturated. We then studied the role of FrzA in several distinct angiogenic models. FrzA induced angiogenesis in a chick chorioallantoic membrane model. Moreover, gene transfer of AdFrzA in grafted mesenchymal and glioma cells increased vessel density and tumor growth. FrzA induced formation of vessels, which were enlarged, longer, and appeared to be more mature compared with vessels formed under control treatments. In vitro, FrzA increased migration and tube formation of endothelial cells and seemed to protect them from apoptosis. FrzA-angiogenic effect in vitro was independent of vascular endothelial growth factor, fibroblast growth factor-2, or angiopiotin-1 induction and Akt activation. In contrast, FrzA decreased glycogen synthase kinase-3 phosphorylation.Conclusions-These results showed that FrzA has proangiogenic effects and suggest that Writ signaling may be involved in normal differentiation as well as in the pathological development of vasculature.