Quantitative Proteomics Reveals the Development of HBV- Associated Glomerulonephritis Triggered by the Downregulation of SLC7A7
Quantitative Proteomics Reveals the Development of HBV- Associated Glomerulonephritis Triggered by the Downregulation of SLC7A7
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定量蛋白质组学揭示 SLC7A7 下调引发 HBV 相关肾小球肾炎的发生
DOI：
10.1021/acs.jproteome.9b00799
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发表时间：
2020
影响因子：
4.4
通讯作者：
Xu Ping
中科院分区：
文献类型：
--
作者：
Zuo Tao;Chen Peiru;Jing Sha;Zhang Tao;Chang Lei;Xu Feng;Zhao Chao;Xu Ping
B型肝炎病毒（hepatitis B virus，HBV）是一种嗜肝DNA病毒，可引起肝外器官损害。肾脏是最容易受到损害的器官之一。关于乙型肝炎病毒相关肾小球肾炎（HBV-GN）的研究已经进行了几十年。然而，潜在的分子机制仍然不清楚。本研究应用串联质量标签（TMT）同量异位素标记法对HBV转基因小鼠肾脏蛋白质组进行定量分析，以阐明HBV-GN的病理机制。加权相关网络分析是一种基因表达的聚类方法，用于蛋白质的聚类。总共，我们在总共5169种定量蛋白质中鉴定了127种与HBV表达高度相关的蛋白质。其中，下调的溶质载体（SLC）家族蛋白参与了HBV-GN的过程。我们还发现IL 1B在HBV转基因小鼠的肾组织中上调。这些发现表明，HBV破坏了肾脏的小分子转运网络，这有助于HBV-GN的发生。转运蛋白，特别是SLC家族7成员7（SLC 7A 7），参与了这一过程，这可能是HBV-GN的干预目标。所有MS数据均已通过iProX合作伙伴存储库存放到ProteomeXchange Consortium，数据集标识符为PXD 016450。
As a hepadnavirus, hepatitis B virus (HBV) can cause damage to extrahepatic organs. The kidney is one of the organs that is more susceptible to damage. Research studies on HBV-associated glomerulonephritis (HBV-GN) have been going on for decades. However, the underlying molecular mechanism remains obscure. Here, we applied a tandem mass tag (TMT) isobaric labeling-based method to quantitatively profile the kidney proteome of HBV transgenic mice to illustrate the pathological mechanisms of HBV-GN. Weighted correlation network analysis, a clustering method for gene expression, is used to cluster proteins. Totally, we identified 127 proteins that were highly associated with HBV expression out of a total of 5169 quantified proteins. Among them, the downregulated solute carrier (SLC) family proteins are involved in the process of HBV-GN. We also found that IL1B was upregulated in the kidney tissue of HBV transgenic mice. These findings suggest that HBV disrupts the small molecule transport network of the kidney, which contributes to the occurrence of HBV-GN. The transporter, particularly SLC family 7 member 7 (SLC7A7), is involved in this process, which might serve as an intervention target for HBV-GN. All MS data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the data set identifier PXD016450.