A comparative proteomic study of nephrogenesis in intrauterine growth restriction
A comparative proteomic study of nephrogenesis in intrauterine growth restriction
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DOI：
10.1007/s00467-009-1437-x
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发表时间：
2010-02
影响因子：
3
通讯作者：
Q. Shen;Hong Xu;Liming Wei;Jing Chen;Hai-mei Liu;W. Guo
中科院分区：
文献类型：
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作者：
Q. Shen;Hong Xu;Liming Wei;Jing Chen;Hai-mei Liu;W. Guo
肾发生需要许多因素的良好平衡，这些因素可被宫内生长受限（IUGR）干扰，导致肾单位禀赋降低。本研究的目的是通过比较蛋白质组学方法来验证IUGR影响调节肾发生的关键蛋白表达的假设。在Sprague-Dawley（SD）大鼠中，通过对妊娠母鼠进行等热量蛋白限制来诱导IUGR。采用双向凝胶电泳、银染、质谱和数据库检索等方法进行分析。银染后，2-DE图像分析显示IUGR组平均730 ± 58个斑点，对照组平均711 ± 73个斑点。平均匹配率分别为86%和81%。差异蛋白质组学分析发现，11个蛋白质点仅在IUGR组中表达，1个在对照组中表达。与对照组相比，IUGR组有7个蛋白点表达上调5倍以上，2个蛋白点表达下调5倍以上。这21个蛋白质点初步鉴定为结构分子，包括波形蛋白、串珠素、γ-肌动蛋白和细胞角蛋白10、转录调节蛋白、转运蛋白、酶等，主要参与能量代谢、氧化还原、信号转导、细胞增殖和凋亡。本研究结果为IUGR肾发育异常的发生机制提供了部分证据，即代谢异常、氧化还原和凋亡失衡、细胞信号和细胞增殖障碍可能是IUGR肾发育异常的主要机制。
Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. The aim of this study was to test the hypothesis that IUGR affects expression of key proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR was induced in Sprague–Dawley (SD) rats by isocaloric protein restriction in pregnant dams. A series of methods, including two-dimensional gel electrophoresis (2-DE), silver staining, mass spectrometry and database searching was used. After silver staining, 2-DE image analysis detected an average 730 ± 58 spots in the IUGR group and 711 ± 73 spots in the control group. The average matched rate was 86% and 81%, respectively. The differential proteomic expression analysis found that 11 protein spots were expressed only in the IUGR group and one in the control group. Seven protein spots were up-regulated more than fivefold and two were down-regulated more than fivefold in the IUGR group compared with those in control group. These 21 protein spots were preliminarily identified and were structural molecules, including vimentin, perlecan, gamma-actin and cytokeratin 10, transcription regulators, transporter proteins, enzymes, and so on. These proteins were involved primarily in energy metabolism, oxidation and reduction, signal transduction, cell proliferation and apoptosis. Data from this study may provide, at least partly, evidence that abnormality of metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and cell proliferation may be the major mechanisms responsible for abnormal nephrogenesis in IUGR.