Kasai Atsushi, Shintani Norihito, Oda Maki, Kakuda Michiya, Hashimoto Hitoshi, Matsuda Toshio, Hinuma Shuji, Baba Akemichi
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Biochem Biophys Res Commun. 2004 Dec 10;325(2):395-400. doi: 10.1016/j.bbrc.2004.10.042.
There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems. We report a new function of apelin as a novel angiogenic factor in retinal endothelial cells. The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA. In accordance with these observations, apelin at concentrations of 1 pM-1 microM significantly enhanced migration, proliferation, and capillary-like tube formation of RF/6A cells, but not those of HUVECs, whereas VEGF stimulates those parameters of both cell types. In vivo Matrigel plug assay for angiogenesis, the inclusion of 1 nM apelin in the Matrigel resulted in clear capillary-like formations with an increase of hemoglobin content in the plug. This is the first report showing that apelin is an angiogenic factor in retinal endothelial cells.
孤儿G蛋白偶联受体APJ的内源性配体apelin在心血管系统和中枢神经系统中的潜在功能近来备受关注。我们报道了apelin作为视网膜内皮细胞中一种新型血管生成因子的新功能。视网膜内皮细胞系RF/6A同时高度表达apelin和APJ转录本,而人脐静脉内皮细胞(HUVECs)仅表达apelin mRNA。与这些观察结果一致,浓度为1 pM - 1 microM的apelin显著增强了RF/6A细胞的迁移、增殖及类毛细血管管腔形成,但对HUVECs无此作用,而血管内皮生长因子(VEGF)可刺激这两种细胞类型的上述参数。在体内进行的用于血管生成的基质胶栓试验中,基质胶中加入1 nM apelin可导致明显的类毛细血管形成,且栓子中的血红蛋白含量增加。这是首份表明apelin是视网膜内皮细胞血管生成因子的报告。