Otani A, Takagi H, Oh H, Koyama S, Honda Y
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Diabetes. 2001 Apr;50(4):867-75. doi: 10.2337/diabetes.50.4.867.
Recent studies have shown that angiopoietins (Angs) and their receptor, Tie2, play a role in vascular integrity and neovascularization. The renin-angiotensin system has been hypothesized to contribute to the development of diabetic retinopathy. In this study, we investigated the effect of angiotensin II (AII) on Ang1 and Ang2 expression in cultured bovine retinal endothelial cells (BRECs). AII stimulated Ang2 but not Ang1 mRNA expression in a dose- and time-dependent manner. This response was inhibited completely by angiotensin type 1 receptor (AT1) antagonist. AII increased the transcription of Ang2 mRNA, but did not change the half-life. Protein kinase C (PKC) inhibitor completely inhibited AII-induced Ang2 expression, and the mitogen-activated protein kinase (MAPK) inhibitor also inhibited it by 69.4+/-15.6%. In addition, we confirmed the upregulation of Ang2 in an AII-induced in vivo rat corneal neovascularization model. These data suggest that AII stimulates Ang2 expression through AT1 receptor-mediated PKC and MAPK pathways in BREC, and AII may play a novel role in retinal neovascularization.
近期研究表明，血管生成素（Angs）及其受体Tie2在血管完整性和新生血管形成中发挥作用。肾素-血管紧张素系统被认为与糖尿病视网膜病变的发生有关。在本研究中，我们调查了血管紧张素II（AII）对培养的牛视网膜内皮细胞（BRECs）中Ang1和Ang2表达的影响。AII以剂量和时间依赖性方式刺激Ang2而非Ang1的mRNA表达。这种反应被1型血管紧张素受体（AT1）拮抗剂完全抑制。AII增加了Ang2 mRNA的转录，但未改变其半衰期。蛋白激酶C（PKC）抑制剂完全抑制了AII诱导的Ang2表达，丝裂原活化蛋白激酶（MAPK）抑制剂也抑制了69.4±15.6%。此外，我们在AII诱导的体内大鼠角膜新生血管形成模型中证实了Ang2的上调。这些数据表明，AII通过AT1受体介导的PKC和MAPK途径刺激BRECs中Ang2的表达，并且AII可能在视网膜新生血管形成中发挥新作用。
