Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation
Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation
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DOI：
10.1152/ajprenal.00134.2008
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发表时间：
2008-10-01
影响因子：
4.2
通讯作者：
Lederer, Eleanor D.
中科院分区：
文献类型：
--
作者：
Merchant, Michael L.;Cummins, Timothy D.;Lederer, Eleanor D.
尽管肾结石/结石的发生率接近10%，但它们对整个美国卫生系统来说是巨大的经济负担。虽然肾结石的相对代谢组成是众所周知的，但对肾结石形成的遗传学没有明确的理解，也没有明确的肾结石形成的预后指标。蛋白质组学在肾结石分析中的应用公理化地认为，通过更全面地了解肾结石蛋白质组成，可以深入了解肾结石的病理生物学。我们分析了分离的肾结石基质蛋白质与质谱和免疫组化方法确定158蛋白质的高置信度，其中包括28个常见的蛋白质。丰富的蛋白质包括先前在结石中鉴定的蛋白质和首次在此鉴定的蛋白质，如髓系特异性、整合膜和脂质调节蛋白。所有蛋白质的通路分析表明，最丰富的基质蛋白的一个显着的分数参与炎症过程。这些蛋白质组学结果支持了结石形成诱导细胞炎症反应的假设，并且这种反应的蛋白质组分有助于丰富的结石基质蛋白质组。
Even though renal stones/calculi occur in similar to 10% of individuals, they are an enormous economic burden to the entire US health system. While the relative metabolic composition of renal calculi is generally known, there is no clear understanding of the genetics of renal stone formation, nor are there clear prognostic indicators of renal stone formation. The application of proteomics to the analysis of renal calculi axiomatically holds that insight into renal stone pathobiology can be gained by a more comprehensive understanding of renal calculus protein composition. We analyzed isolated renal stone matrix proteins with mass spectrometric and immunohistochemical methods identifying 158 proteins with high confidence, including 28 common proteins. The abundant proteins included those identified previously in stones and proteins identified here for the first time, such as myeloid lineage- specific, integral membrane and lipid regulatory proteins. Pathway analyses of all proteins identified suggested that a significant fraction of the most abundant matrix proteins participate in inflammatory processes. These proteomic results support the hypothesis that stone formation induces a cellular inflammatory response and the protein components of this response contribute to the abundant stone matrix proteome.