Inflammatory and fibrotic proteins proteomically identified as key protein constituents in urine and stone matrix of patients with kidney calculi
Inflammatory and fibrotic proteins proteomically identified as key protein constituents in urine and stone matrix of patients with kidney calculi
复制标题
DOI：
10.1016/j.cca.2013.11.036
复制
发表时间：
2014-02-15
影响因子：
5
通讯作者：
Krieglstein, Kerstin
中科院分区：
文献类型：
--
作者：
Boonla, Chanchai;Tosukhowong, Piyaratana;Krieglstein, Kerstin
为了发现尿蛋白是否被合并到结石中，必须探索肾结石和从同一患者收集的尿液的蛋白质组学特征。我们用1D-PAGE和纳米高效液相-电喷雾串联质谱仪分析了肾结石基质(n=16)、肾结石尿液(n=14)和正常尿液(n=3)的蛋白质组。我们在结石基质、肾结石患者尿液和正常尿液中分别鉴定出62、66和22种蛋白质。在结石基质和肾结石的尿液中经常检测到炎症和纤维化相关蛋白。18种蛋白质仅在结石基质和肾结石尿中发现，被认为是肾结石形成的候选生物标志物。S100A8和纤维连接蛋白分别代表炎症和纤维化，在肾结石肾组织中表达上调。S100A8在浸润性白细胞中强表达。纤维连接蛋白在肾小管上皮细胞中高表达。S100A8和纤维连接蛋白在肾结石患者的尿液和结石基质中均有表达，而在正常尿液中检测不到。结论：同一患者的肾结石和尿液中均含有大量炎性和纤维化蛋白。S100A8和纤维连接蛋白在结石肾和肾结石尿液中表达上调。因此，炎症和纤维化被认为参与了肾结石的形成。(C)2013爱思唯尔B.V.保留所有权利。
To uncover whether urinary proteins are incorporated into stones, the proteomic profiles of kidney stones and urine collected from the same patients have to be explored. We employed 1D-PAGE and nanoHPLC-ESI-MS/MS to analyze the proteomes of kidney stone matrix (n = 16), nephrolithiatic urine (n = 14) and healthy urine (n = 3). We identified 62, 66 and 22 proteins in stone matrix, nephrolithiatic urine and healthy urine, respectively. Inflammation- and fibrosis-associated proteins were frequently detected in the stone matrix and nephrolithiatic urine. Eighteen proteins were exclusively found in the stone matrix and nephrolithiatic urine, considered as candidate biomarkers for kidney stone formation. S100A8 and fibronectin, representatives of inflammation and fibrosis, respectively, were up-regulated in nephrolithiasis renal tissues. S100A8 was strongly expressed in infiltrated leukocytes. Fibronectin was over-expressed in renal tubular cells. S100A8 and fibronectin were immunologically confirmed to exist in nephrolithiatic urine and stone matrix, but in healthy urine they were undetectable. Conclusion, both kidney stones and urine obtained from the same patients greatly contained inflammatory and fibrotic proteins. S100A8 and fibronectin were up-regulated in stone-baring kidneys and nephrolithiatic urine. Therefore, inflammation and fibrosis are suggested to be involved in the formation of kidney calculi. (C) 2013 Elsevier B.V. All rights reserved.