Comparison of cat and human calcium oxalate monohydrate kidney stone matrix proteomes.
Comparison of cat and human calcium oxalate monohydrate kidney stone matrix proteomes.
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DOI：
10.1007/s00240-022-01363-w
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发表时间：
2022-12
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影响因子：
3.1
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中科院分区：
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尽管基质具有危害性，但它在草酸钙结石形成中的作用却鲜为人知。构成基质的蛋白质种类繁多，这也是造成这种不确定的原因之一。这项研究比较了用质谱仪测量的人类草酸钙结石基质中的蛋白质分布与猫结石基质中观察到的蛋白质分布，因为猫与人类有许多共同的结石疾病的临床特征。观察到的蛋白质分布是在最近一个基于强阴离子和强阳离子蛋白质聚集的模型的背景下进行分析的，该模型包括基于总电荷的对其他蛋白质的选择性吸附。基质蛋白在物种间的分布有许多共同的特征，包括富含强阴离子和强阳离子蛋白，基质蛋白中的总电荷比尿蛋白增加，以及两种物种基质中突出的强阴离子蛋白具有高度的相似性。然而，在净电荷分布的其他区域，特定优势蛋白的重叠较弱。总的来说，这些观察结果支持概念模型，即强阴离子蛋白质与草酸钙晶体表面结合最强，而其他蛋白质通过非特异性电荷相互作用与强阴离子蛋白质结合形成结石。此外，根据这些相似性，猫似乎是迄今为止确定的最好的人类结石疾病动物模型。
Despite its critical nature, the role of matrix in calcium oxalate stone formation is poorly understood. The wide diversity of proteins comprising matrix has contributed to the ambiguity. This study compares the protein distributions measured by mass spectrometry in human calcium oxalate stone matrix to that observed in cat stone matrix, because cats share many clinical characteristics of their stone disease with humans. The observed protein distributions were analyzed in the context of a recent model based on the aggregation of strongly anionic and strongly cationic proteins which includes selective adsorption of other proteins based on total charge. Matrix protein distributions shared many common features between species, including enrichment of both strongly anionic and strongly cationic proteins, increased total charge in matrix proteins compared to urine proteins, and a high degree of similarity of prominent strongly anionic proteins in the matrix of both species. However, there was weaker overlap of the specific dominant proteins in other regions of the net charge distribution. Collectively, these observations support the conceptual model where the strongly anionic proteins associate most strongly with the calcium oxalate crystal surfaces, while the other proteins associate with the strongly anionic proteins through non-specific, charge interactions with each other to create stones. Also, cats appear to be the best animal model of human stone disease identified to date based on these similarities.