Bioinformatics Analysis of Proteomic Profiles During the Process of Anti-Thy1 Nephritis
Bioinformatics Analysis of Proteomic Profiles During the Process of Anti-Thy1 Nephritis
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抗Thy1肾炎过程中蛋白质组谱的生物信息学分析
DOI：
10.1074/mcp.m111.008755
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发表时间：
2012-04-01
影响因子：
7
通讯作者：
Chen, Xiangmei
中科院分区：
文献类型：
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作者：
Lu, Yang;Liu, Xiaoluan;Chen, Xiangmei
抗Thy 1肾炎是一种成熟的实验性系膜增生性肾炎模型。探讨抗Thy 1肾炎的分子病理生理机制可能有助于阐明系膜增生的发病机制。通过对抗Thy 1肾炎肾小球蛋白质组的生物信息学分析，探讨了差异表达蛋白在抗Thy 1肾炎发病过程中的作用及作用机制。结果表明，共分离到108个DEPs，其中40个DEPs经基质辅助激光解吸电离/飞行时间和液相色谱-质谱联用技术鉴定（聚类1-5），根据它们的表达趋势，使用聚类3.0软件，参与调节生物过程，如应激反应，细胞增殖、凋亡、能量代谢、转运和肌动蛋白细胞骨架。通过Western blotting验证了10种DEP的表达模式，分布在5个簇中，包括AKR 1A 1，AGAT，ATP 6V 1B 2，HIBADH，MDH 1，MPST，NIT 2，PRDX 6，PSMB 7和TPI 1。Western blotting和免疫组化结果显示，DEP FHL 2主要表达于肾小球系膜区，在第3、5天表达下调，第10天表达上调。在体外实验中，我们发现FHL 2过表达通过增加S期细胞数量和减少G2/M期细胞数量来诱导系膜细胞增殖，而抑制FHL 2则具有相反的效果。本研究探讨了新的DEPs及其在抗Thy 1肾炎中的表达模式，并阐明了FHL 2对系膜细胞增殖的影响。这些结果将有助于我们了解系膜增生的发病机制。Molecular & Cellular Proteomics 11：10.1074/mcp.M111.008755，1-13，2012.
Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expressed proteins (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were identified by matrix-assisted laser desorption ionization/time of flight and liquid chromatography-MS. DEPs were classified into five clusters (Clusters 1-5), according to their expression trends using Cluster 3.0 software, involved in regulating biological processes such as the stress response, cell proliferation, apoptosis, energy metabolism, transport, and the actin cytoskeleton. The expression patterns of ten DEPs, distributed across five clusters, including AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were validated by Western blotting. Based on Western blotting and immunohistochemistry, we also found that the DEP FHL2, which was primarily expressed in the mesangial region, was down-regulated on days 3 and 5, and up-regulated on day 10. In vitro, we found that FHL2 overexpression induced mesangial cell proliferation by increasing the number of S-phase cells and decreasing G2/M-phase cells, whereas inhibiting FHL2 had the opposite effect. This study explored novel DEPs and their expression patterns during anti-Thy1 nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These results will contribute to our understanding of the pathogenesis of mesangial proliferation. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.008755, 1-13, 2012.