Regulation of Fibroblast Growth Factor 2 Expression in Oxygen-Induced Retinopathy
Regulation of Fibroblast Growth Factor 2 Expression in Oxygen-Induced Retinopathy
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DOI：
10.1167/iovs.14-15616
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Shenberger, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Fang, Li;Barber, Alistair J.;Shenberger, Jeffrey S.
目的.成纤维细胞生长因子（FGF）2是一种有效的内皮细胞有丝分裂原和存活因子，被认为参与早产儿视网膜病变（ROP）的发病机制。本研究的目的是确定在氧诱导视网膜病变（OIR），ROP的动物模型的FGF 2表达的转录和翻译调控。我们检测了在转基因小鼠中FGF 2蛋白和mRNA的表达以及视动视觉反应，所述转基因小鼠具有含有FGF 2的50个内部核糖体进入位点（IRES）的双荧光素酶双顺反子转基因。我们发现，视网膜FGF 2蛋白亚型的表达随年龄而变化，但不响应OIR。荧光素酶，蛋白质和mRNA的数据分析表明，FGF 2蛋白表达抑制在血管闭塞阶段的OIR，可能通过抑制延长。在从血管闭塞到新血管形成的过渡中，FGF 2蛋白表达的增加对应于IRES活性的维持和帽依赖性翻译活性的降低。在新生血管形成过程中，FGF 2的表达主要受转录调控。从OIR恢复的小鼠在6周龄时显示视觉视动反应的改变和增加的FGF 2蛋白表达。总之，这些发现说明了复杂的翻译和转录调控的FGF 2蛋白表达OIR。增强的FGF 2表达和减少视动反应的决议过程中的表面血管病变可能表明在OIR/ROP的神经视网膜功能的维护中的FGF 2的作用。
PURPOSE. Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is postulated to participate in the pathogenesis of retinopathy of prematurity (ROP). The purpose of the current study was to determine the transcriptional and translational regulation of FGF2 expression in oxygen-induced retinopathy (OIR), the animal model of ROP.METHODS. We examined FGF2 protein and mRNA expression and optokinetic visual responses in transgenic mice possessing a dual-luciferase bicistronic transgene containing a 50-internal ribosome entry site (IRES) of FGF2.RESULTS. We found that retinal FGF2 protein isoform expression varies with age but not in response to OIR. Analysis of luciferase, protein, and mRNA data indicate that FGF2 protein expression is translationally repressed during the vaso-obliterative phase of OIR, possibly by inhibiting elongation. At the transition from vaso-obliteration to neovascularization, heightened FGF2 protein expression corresponds to maintenance of IRES activity and diminished cap-dependent translational activity. During neovascularization, FGF2 expression is primarily regulated by transcription. Mice recovering from OIR display alterations in visual optokinetic responses and increased FGF2 protein expression at 6 weeks of age.CONCLUSIONS. In total, these findings illustrate the complexity of translational and transcriptional regulation of FGF2 protein expression in OIR. The augmentation of FGF2 expression and reduced optokinetic responses during the resolution of surface vasculopathy may indicate a role for FGF2 in the maintenance of neuroretinal function in OIR/ROP.