VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats
VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats
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DOI：
10.1172/jci33673
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发表时间：
2008-03-01
影响因子：
15.9
通讯作者：
Li, Xuri
中科院分区：
文献类型：
--
作者：
Li, Yang;Zhang, Fan;Li, Xuri
尽管VEGF-B发现较早且与其他VEGF家族成员具有高度同源性，但其生物学功能仍知之甚少。我们揭示了VEGF-B作为一种有效的细胞凋亡抑制剂的新功能。使用小鼠主动脉平滑肌细胞的基因表达谱，并确认使用小鼠和大鼠细胞细粉的实时PCR的结果，我们表明，VEGF-B抑制编码促凋亡BH 3蛋白和其他凋亡和细胞死亡相关蛋白，包括p53和caspase家族成员的基因的表达，通过激活VEGFR-1。与此一致，VEGF-B治疗分别在眼部神经变性疾病和中风的小鼠模型中拯救视网膜和脑中的神经元免于凋亡。有趣的是，在对神经元存活有效的剂量下的VEGF-B治疗没有引起视网膜新生血管形成，这表明VEGF-B是VEGF家族的第一个成员，其具有有效的抗凋亡作用，同时缺乏一般的血管生成活性。这些发现表明VEGF-B可能为治疗神经退行性疾病提供新的治疗选择。
Despite its early discovery and high sequence homology to the other VEGF family members, the biological functions of VEGF-B remain poorly understood. We revealed here a novel function for VEGF-B as a potent inhibitor of apoptosis. Using gene expression profiling of mouse primary aortic smooth muscle cells, and confirming the results by real-time PCR using mouse and rat cell fines, we showed that VEGF-B inhibited the expression of genes encoding the proapoptotic BH3-only proteins and other apoptosis- and cell death-related proteins, including p53 and members of the caspase family, via activation of VEGFR-1. Consistent with this, VEGF-B treatment rescued neurons from apoptosis in the retina and brain in mouse models of ocular neurodegenerative disorders and stroke, respectively. Interestingly, VEGF-B treatment at the dose effective for neuronal survival did not cause retinal neovascularization, suggesting that VEGF-B is the first member of the VEGF family that has a potent antiapoptotic effect while lacking a general angiogenic activity. These findings indicate that VEGF-B may potentially offer a new therapeutic option for the treatment of neurodegenerative diseases.