Characterization of the renal cyst fluid proteome in autosomal dominant polycystic kidney disease (ADPKD) patients.
Characterization of the renal cyst fluid proteome in autosomal dominant polycystic kidney disease (ADPKD) patients.
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DOI：
10.1002/prca.200780140
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发表时间：
2008-07-01
影响因子：
2
通讯作者：
Witzmann, Frank A.
中科院分区：
文献类型：
--
作者：
Lai, Xianyin;Bacalla, Robert L.;Blazer-Yost, Bonnie L.;Hong, David;Mason, Stephen B.;Witzmann, Frank A.
常染色体显性多囊肾病（ADPKD）的特征是局部自主性细胞增殖、囊肿内液体积聚以及肾脏实质内纤维化。对于囊肿液的蛋白质组成知之甚少。我们假设囊肿液蛋白质的复杂集合（囊肿液蛋白质组）在囊肿形成/维持中起主要作用，并且包含所有形式的多囊肾病（PKD）共有的尚未知晓的诊断和机制特征。我们分析了来自4名ADPKD患者的5种肾囊肿液。通过液相色谱 - 串联质谱（LC - MS/MS）分析了来自血浆蛋白免疫耗竭（ProteoPrep®）和未耗竭囊肿液样本的胰蛋白酶肽段。通过SEQUEST™鉴定蛋白质，并通过跨蛋白质组学流程进行验证；以>90%的置信度鉴定出391种蛋白质；其中251种在未耗竭样本中，362种在免疫耗竭样本中。免疫耗竭去除了>94%的囊肿液蛋白质。鉴定出了大多数囊肿共有的数量惊人且功能多样的蛋白质。这些蛋白质可能具有机制研究意义，包括Igγ、κ及其片段；补体成分；玻连蛋白；α - 酸性糖蛋白；前列腺素D2合酶；维生素D结合蛋白；簇集素；丝氨酸蛋白酶抑制剂（SERPIN）家族蛋白质；血红素结合蛋白；以及胎球蛋白 - A。此外，这些结果表明，对胰蛋白酶肽段进行进一步的预分级和增强色谱分离可能会揭示更多相关蛋白质。
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by localized autonomous cellular proliferation, fluid accumulation within the cysts, and intraparenchymal fibrosis of the kidney. Little is known about the cyst fluid's protein composition. We hypothesized that the complex collection of cyst fluid proteins (cyst fluid proteome) plays a major role in cyst formation/maintenance and contains yet unknown diagnostic and mechanistic features that are common to all forms of PKD. We analyzed five kidney cyst fluids from four patients with ADPKD. Tryptic peptides from plasma-protein immunodepleted (ProteoPrep®) and undepleted cyst fluid samples were analyzed by LC-MS/MS. Proteins were identified by SEQUEST™ and validated via the Trans-Proteomic Pipeline; 391 proteins were identified with >90% confidence; 251 of them in undepleted and 362 in immunodepleted samples. Immunodepletion removed >94% of the cyst fluid protein. A surprisingly large and functionally diverse number of proteins common to most cysts were identified. These proteins may be of mechanistic interest and include Ig γ, κ, and fragments; complement components; vitronectin; orosomucoid; prostaglandin D2 synthase; vitamin D-binding protein; clusterin; SERPIN family proteins; hemopexin; and fetuin-A. Additionally, these results suggest that further prefractionation and enhanced chromatographic separation of tryptic peptides is likely to expose an even greater number of relevant proteins.
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影响因子：
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Mochizuki, T;Wu, GQ;Somlo, S
通讯作者：
Somlo, S
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EVERSON, GT;EMMETT, M;THICKMAN, D
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