Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina.
Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina.
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DOI：
10.1038/s41598-018-34955-x
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发表时间：
2018-11-13
影响因子：
4.6
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Saddala MS;Lennikov A;Grab DJ;Liu GS;Tang S;Huang H
胎盘生长因子（PlGF或PGF）是血管内皮生长因子（VEGF）亚家族的成员，在病理性血管生成和炎症中起着至关重要的作用。然而，PlGF介导的非增殖性糖尿病视网膜病变（DR）并发症的潜在分子机制尚不清楚。使用LC-MS/MS-based无标记定量蛋白质组学方法，我们表征了C57BL6、秋田、PlGF−/−和秋田获得的视网膜中PlGF消蚀引起的蛋白质表达变化。PlGF−−老鼠。经胰蛋白酶/LysC酶切提取后，采用Q-Exactive杂交四极轨道阱质谱法对视网膜蛋白进行分析。根据Z-score归一化和Pearson相关系数的可重复性，在4个比较中鉴定出差异表达蛋白（DEPs）。基因本体（GO）、功能通路和蛋白-蛋白网络相互作用分析表明，参与胰岛素抵抗通路的几种蛋白（Gnb1、Gnb2、Gnb4、Gnai2、Gnao1、Snap2和Gngt1）在PlGF切除的秋田糖尿病小鼠中显著下调(Akita；PlGF−/−vs.秋田)，但在秋田vs. C57和PlGF−/−vs. C57条件下上调。两种参与抗氧化活性和神经保护通路的蛋白Prdx6和Map2在秋田上调。PlGF−/−vs.秋田条件。总之，我们预测胰岛素抵抗必需蛋白的下调，以及抗氧化和神经保护蛋白的上调，突出并概括了未来抗plgf治疗DR的重要潜在机制。
Placental growth factor (PlGF or PGF), a member of the vascular endothelial growth factor (VEGF) sub-family, plays a crucial role in pathological angiogenesis and inflammation. However, the underlying molecular mechanisms that PlGF mediates regarding the complications of non-proliferative diabetic retinopathy (DR) remain elusive. Using an LC-MS/MS-based label-free quantification proteomic approach we characterized the alterations in protein expression caused by PlGF ablation in the retinas obtained from C57BL6, Akita, PlGF−/− and Akita.PlGF−/− mice. After extraction and enzymatic digestion with Trypsin/LysC, the retinal proteins were analyzed by Q-Exactive hybrid Quadrupole-Orbitrap mass spectrometry. Differentially expressed proteins (DEPs) were identified in four comparisons based on Z-score normalization and reproducibility by Pearson’s correlation coefficient. The gene ontology (GO), functional pathways, and protein-protein network interaction analysis suggested that several proteins involved in insulin resistance pathways (Gnb1, Gnb2, Gnb4, Gnai2, Gnao1, Snap2, and Gngt1) were significantly down-regulated in PlGF ablated Akita diabetic mice (Akita.PlGF−/− vs. Akita) but up-regulated in Akita vs. C57 and PlGF−/− vs. C57 conditions. Two proteins involved in the antioxidant activity and neural protection pathways, Prdx6 and Map2 respectively, were up-regulated in the Akita.PlGF−/− vs. Akita condition. Overall, we predict that down-regulation of proteins essential for insulin resistance, together with the up-regulation of antioxidant and neuroprotection proteins highlight and epitomize the potential mechanisms important for future anti-PlGF therapies in the treatment of DR.
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