Reduced β-2-glycoprotein I inhibits hypoxia-induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway
Reduced β-2-glycoprotein I inhibits hypoxia-induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway
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DOI：
10.3892/mmr.2014.2869
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Yu, Pei
中科院分区：
文献类型：
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作者：
Liu, Hongyan;Zhou, Saijun;Yu, Pei
β-2-糖蛋白I（β 2GPI），也称为载脂蛋白H，是由五个同源重复单元组成的磷脂结合血浆蛋白。β 2 GPI在体外下调血管内皮生长因子（VEGF）信号通路并抑制血管生成。然而，在视网膜血管生成中，降低的β 2GPI和β 2GPI的体内作用和效应物仍然没有完全理解。本研究采用氧诱导的视网膜病变模型，观察β 2 GPI和β 2 GPI降低对视网膜病变的影响，并检测VEGF、VEGF受体（VEGFR）1、VEGFR-2和缺氧诱导因子1（HIF-1）mRNA的表达以及细胞外信号调节激酶（ERK）和Akt的磷酸化。结果表明，β 2GPI和还原型β 2GPI均能抑制视网膜血管新生，抑制VEGF、VEGFR-1、VEGFR-2、HIF-1、磷酸化ERK和p-Akt的表达。降低的β 2GPI的作用明显强于β 2GPI。总之，本研究表明，β 2GPI和还原型β 2GPI可以通过下调VEGF及其下游靶点的表达来抑制视网膜血管生成。这表明β 2GPI和还原的β 2GPI可能具有潜在的体内抗血管生成活性。
beta-2-glycoprotein I (beta 2GPI), also known as apolipoprotein H, is a phospholipid-binding plasma protein consisting of five homologous repeated units. beta 2GPI downregulates vascular endothelial growth factor (VEGF) signaling pathways and inhibits angiogenesis in vitro. However, the in vivo roles and effectors of reduced beta 2GPI and beta 2GPI in retinal angiogenesis are still not fully understood. In this study, an oxygen-induced retinopathy model was used to investigate the effects of reduced beta 2GPI and beta 2GPI, and to monitor the expression of VEGF, VEGF receptor (VEGFR) 1, VEGFR-2 and hypoxia-inducible factor 1 (HIF-1) mRNA and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. The data showed that both beta 2GPI and reduced beta 2GPI inhibited retinal angiogenesis and suppressed the expression of VEGF, VEGFR-1, VEGFR-2, HIF-1, phosphorylated- (p-) ERK and p-Akt. The effects of reduced beta 2GPI were significantly stronger than those of beta 2GPI. In conclusion, this study showed that beta 2GPI and reduced beta 2GPI could inhibit retinal angiogenesis by downregulating the expression of VEGF and its downstream targets. This suggests that beta 2GPI and reduced beta 2GPI may have potential anti-angiogenic activity in vivo.