Proteomic Analysis of Radiation-Induced Acute Liver Damage in a Rabbit Model
Proteomic Analysis of Radiation-Induced Acute Liver Damage in a Rabbit Model
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兔模型中辐射引起的急性肝损伤的蛋白质组学分析
DOI：
10.1177/1559325819889508
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发表时间：
2019-10-01
期刊：
影响因子：
2.5
通讯作者：
Zhang，Shuyu
中科院分区：
文献类型：
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作者：
Jiang，Lingong;Jia，Huimin;Zhang，Shuyu
放射性肝损伤（RILD）已成为肝细胞癌放疗的局限性。我们用射波刀建立了家兔RILD模型。电镜分析显示辐照后核明显萎缩，核内脂肪分布明显。然后，我们利用基于质谱的无标记相对定量蛋白质组学方法来比较兔肝脏对辐射响应的整体蛋白质组学变化。总共鉴定出2365种蛋白质，其中338种蛋白质在辐照和未辐照的肝组织中显著失调。这些差异表达蛋白包括USP47、POLR2A、CSTB、MCFD2和CSNK2A1。实时聚合酶链反应证实，USP47和CABLES1转录本在辐照肝组织中显著升高，而MCFD2和CSNK2A1的表达显著降低。在cluster of Orthologous Groups of proteins分析中，对差异表达蛋白进行了注释，并将其分为24类，包括翻译后修饰、蛋白周转和伴侣蛋白。京都基因与基因组百科分析显示，失调蛋白的富集通路包括血管内皮生长因子（VEGF）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路和脂肪细胞因子信号通路。蛋白质和途径的鉴定对于阐明肝脏的辐射反应过程至关重要，这可能有助于发现新的治疗靶点。
Radiation-induced liver damage (RILD) has become a limitation in radiotherapy for hepatocellular carcinoma. We established a rabbit model of RILD by CyberKnife. Electron microscopy analysis revealed obvious nuclear atrophy and disposition of fat in the nucleus after irradiation. We then utilized a mass spectrometry-based label-free relative quantitative proteomics approach to compare global proteomic changes of rabbit liver in response to radiation. In total, 2365 proteins were identified, including 338 proteins that were significantly dysregulated between irradiated and nonirradiated liver tissues. These differentially expressed proteins included USP47, POLR2A, CSTB, MCFD2, and CSNK2A1. Real-time polymerase chain reaction confirmed that USP47 and CABLES1 transcripts were significantly higher in irradiated liver tissues, whereas MCFD2 and CSNK2A1 expressions were significantly reduced. In Clusters of Orthologous Groups of proteins analysis, differentially expressed proteins were annotated and divided into 24 categories, including posttranslational modification, protein turnover, and chaperones. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the enriched pathways in dysregulated proteins included the vascular endothelial growth factors (VEGF) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the adipocytokine signaling pathway. The identification of proteins and pathways is crucial toward elucidating the radiation response process of the liver, which may facilitate the discovery of novel therapeutic targets.