Department of Life Science, Graduate School of Engineering Science, Akita University, 1-1 Tegatagakuen-machi, Akita, Akita, 010-8502, Japan.
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan.
Clin Exp Nephrol. 2020 Aug;24(8):666-679. doi: 10.1007/s10157-020-01898-5. Epub 2020 May 20.
High-IgA ddY (HIGA) mice, an animal model of human IgA nephropathy (IgAN), spontaneously develop nephropathy with glomerular IgA deposition and markedly elevated serum IgA levels from 25 weeks of age.
We performed a comparative proteomic analysis of the renal proteins collected from HIGA mice and control C57BL/6 mice at 5 or 38 weeks of age (the H5, H38, C5, and C38 groups) (n = 4 in each group). Proteins were extracted from the left whole kidney of each mouse and analyzed using nano-liquid chromatography-tandem mass spectrometry. The right kidneys were used for histopathological examinations.
Immunohistochemical examinations showed glomerular deposition of IgA and the immunoglobulin joining (J) chain, and increased numbers of interstitial IgA- and J-chain-positive plasma cells in the H38 group. In the proteomic analysis, > 5000 proteins were identified, and 33 proteins with H38/H5 ratios of > 5.0, H38/C38 ratios of > 5.0, and C38/C5 ratios of < 1.5 were selected. Among them, there were various proteins that are known to be involved in human IgAN and/or animal IgAN models. Immunohistochemical examinations validated the proteomic results for some proteins. Furthermore, two proteins that are known to be associated with kidney disease displayed downregulated expression (H38/H5 ratio: 0.01) in the H38 group.
The results of comparative proteomic analysis of renal proteins were consistent with previous histopathological and serological findings obtained in ddY and HIGA mice. Various proteins that are known to be involved in kidney disease, including IgAN, and potential disease marker proteins exhibited markedly altered levels in HIGA mice.
高 IgA ddY（HIGA）小鼠是一种人类 IgA 肾病（IgAN）的动物模型，从 25 周龄开始自发出现肾小球 IgA 沉积和明显升高的血清 IgA 水平。
我们对来自 HIGA 小鼠和对照 C57BL/6 小鼠的 5 或 38 周龄（H5、H38、C5 和 C38 组）（每组 4 只）的肾脏蛋白进行了比较蛋白质组学分析。从每只小鼠的左全肾中提取蛋白质，并使用纳升液相色谱-串联质谱进行分析。右肾用于组织病理学检查。
免疫组织化学检查显示 H38 组肾小球 IgA 和免疫球蛋白连接（J）链沉积，间质中 IgA 和 J 链阳性浆细胞数量增加。在蛋白质组学分析中，鉴定出超过 5000 种蛋白质，选择了 33 种 H38/H5 比值>5.0、H38/C38 比值>5.0 和 C38/C5 比值<1.5 的蛋白质。其中，有各种已知参与人类 IgAN 和/或动物 IgAN 模型的蛋白质。免疫组织化学检查验证了一些蛋白质的蛋白质组学结果。此外，两种已知与肾脏疾病相关的蛋白质在 H38 组中的表达下调（H38/H5 比值：0.01）。
肾脏蛋白比较蛋白质组学分析的结果与 ddY 和 HIGA 小鼠之前的组织病理学和血清学发现一致。各种已知与肾脏疾病（包括 IgAN）相关的蛋白质以及潜在的疾病标志物蛋白质在 HIGA 小鼠中表现出明显改变的水平。
