State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, P. R. China.
National Clinical Research Center for Aging and Medicine, Huashan Hospital & MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
J Proteome Res. 2020 Apr 3;19(4):1556-1564. doi: 10.1021/acs.jproteome.9b00799. Epub 2020 Mar 19.
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.
作为一种嗜肝 DNA 病毒，乙型肝炎病毒 (HBV) 可导致肝外器官损伤。肾脏是易受损伤的器官之一。对乙型肝炎病毒相关性肾小球肾炎 (HBV-GN) 的研究已经进行了几十年。然而，其潜在的分子机制仍不清楚。在这里，我们应用串联质量标签 (TMT) 等压标记定量蛋白质组学方法来描绘 HBV 转基因小鼠的肾脏蛋白质组，以阐明 HBV-GN 的病理机制。加权相关网络分析，一种基因表达聚类方法，用于聚类蛋白质。在总共 5169 个定量蛋白质中，我们鉴定出 127 个与 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 HBV-GN 的发生过程。我们还发现，HBV 转基因小鼠肾脏组织中的 IL1B 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 (SLC7A7)，参与了这一过程，这可能成为 HBV-GN 的干预靶点。所有 MS 数据已通过 iProX 合作伙伴存储库存入 ProteomeXchange 联盟，数据集标识符为 PXD016450。
