Gene expression profiling of peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome by cDNA microarrays
Gene expression profiling of peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome by cDNA microarrays
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DOI：
10.1159/000114098
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Sawada, Ken-ichi
中科院分区：
文献类型：
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作者：
Komatsuda, Atsushi;Wakui, Hideki;Sawada, Ken-ichi
背景：微小病变型肾病综合征(MCNS)被认为是免疫细胞功能障碍导致肾小球通透性因子释放的结果。然而，这些因素的性质仍然不确定。方法：应用基因芯片技术对2例MCNS患者外周血单个核细胞(PBMC)在肾病及缓解期的基因表达谱进行分析。为了验证基因芯片的结果，我们对24例MCNS患者、10例膜性肾病(MN)患者和24例健康人的肾病和缓解期标本进行了实时定量逆转录聚合酶链式反应(RT-PCR)分析。结果：在筛选的24,446个基因中，171个功能已知的基因在肾病期MCNS患者的PBMC中上调(至少2倍)。21个基因编码参与信号转导和细胞因子反应的蛋白。为了进一步研究，我们选择了两个编码可证明的分泌蛋白的基因，趋化因子(C-C)配体13(CCL13)和一个新的Galectin相关蛋白(HSPC159)。定量RT-PCR结果显示，24例MCNS患者的肾病PBMC中CCL13和HSPC159的表达均高于缓解期患者，而10例MN患者中CCL13和HSPC159的表达模式有所不同。肾病MCNS患者PBMC中CCL13和HSPC159的表达明显高于肾病MN患者和正常对照组。结论：肾病期MCNS患者PBMC中CCL13和HSPC159的表达呈特异性上调。这些表达变化是否直接参与MCNS的病理生理过程还需要进一步的研究。版权所有(C)2008 S.Karger AG，巴塞尔。
Background: It is hypothesized that minimal change nephrotic syndrome (MCNS) is a consequence of immune cell dysfunction that may lead to release of glomerular permeability factors. However, the nature of such factors remains uncertain. Methods: Using cDNA microarrays, we performed gene expression profiling of peripheral blood mononuclear cells (PBMC) from 2 MCNS patients during nephrosis and remission phases. To confirm the cDNA microarray results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses in nephrosis and remission samples from 24 MCNS patients and 10 patients with membranous nephropathy (MN), and from 24 healthy subjects. Results: Out of 24,446 genes screened, 171 functionally known genes were up-regulated ( at least 2-fold) in PBMC from MCNS patients during the nephrosis phase. 21 genes encoded proteins involved in signal transduction and cytokine response. For further examination, we selected two genes encoding provable secretory proteins, chemokine (C-C) ligand 13 (CCL13) and a novel galectin-related protein (HSPC159). The results of quantitative RT-PCR showed that expressions of CCL13 and HSPC159 mRNA in nephrosis PBMC samples were higher than those in remission samples from all 24 MCNS patients examined, while these mRNA expression patterns were variable among 10 MN patients. CCL13 and HSPC159 mRNA expressions in PBMC from MCNS patients in nephrosis were significantly higher than those in nephrotic MN patients and healthy controls. Conclusion: We found that CCL13 and HSPC159 mRNA expressions in PBMC are up-regulated specifically in MCNS patients during the nephrosis phase. Further studies are necessary to clarify whether these expression changes are directly involved in the pathophysiologic processes of MCNS. Copyright (C) 2008 S. Karger AG, Basel.