基于蛋白质组学的尿液中肾脏疾病相关蛋白的筛选

Screening of urinary disease-related proteins in patients with kidney disease based on proteomics data analysis

目的:通过对正常人血浆、尿液、肾组织及肾脏疾病患者尿液蛋白质组学获取的数据进行比较分析,寻找尿液中与肾脏疾病及肾脏损伤相关的生物标志物。方法:肾脏疾病患者尿液蛋白质组数据来自表现为肾病综合征的膜性肾病(MN)和局灶节段性肾小球硬化(FSGS)患者尿液蛋白质组谱图,从Peptide Atlas 2013数据库获得正常人血浆、尿液和肾组织蛋白质组数据。寻找肾脏疾病患者尿液蛋白质组相对正常人尿液蛋白质组富集蛋白,将筛选到的蛋白定义为肾脏疾病相关蛋白。寻找正常人血浆和尿液蛋白质组中不出现,同时在肾脏疾病患者尿液和肾组织蛋白质组中出现,且相对正常人尿液蛋白质组富集的蛋白,将筛选到的蛋白定义为肾损伤相关蛋白。结果:筛选到40种肾脏疾病相关蛋白。发现4种与肾损伤相关的蛋白,分别为泛素-60s核糖体蛋白L40、S相激酶相关蛋白1、转化生长因子βⅡ型受体、谷胱甘肽S转移酶A3。结论:通过对肾脏疾病患者尿液蛋白质组学数据与正常人血浆、尿液和肾组织的蛋白质组学数据进行比较分析,从患者尿液中获得了40种与肾脏疾病相关的蛋白和4种肾脏组织损伤相关的蛋白。上述蛋白成分在肾脏疾病诊断及病情判断中的意义有待进一步研究阐明。

Objective：To explore kidney disease-related proteins and kidney damage-related proteins in urine of patients with kidney disease. Methodology： Urine proteomic data of patients with kidney disease came from urine proteomic profiles of FSGS and MN with nephrotic syndrome. Plasma, urine and kidney proteomic data of healthy subjects were obtained from Peptide Atlas 2013. The data from urine proteomic of patients with kidney disease were compared to the data from plasma, urine and kidney proteomic of healthy subjects. The proteins which enriched in urine proteomic of patients with kidney disease to urine proteomic of healthy subjects were named by kidney disease-related protein. Coincidence analysis for above four proteomics was made to search kidney damage-related proteins which are not in plasma proteomic of healthy subjects, shared in urine proteomic of patients with kidney disease and kidney proteomic of healthy subjects, and enriched in urine proteomie of patients with kidney disease to urine proteomie of healthy subjects. Results ： A total of 40 kidney disease-related proteins and 4 kidney damage-related proteins, Ubiquitin-60S ribosomal protein L40, S-phase kinase-associated protein 1, TGF-beta receptor type-2 and Glutathione S-transferase A3 was found. Conclusion： By comparing data from above four proteomic, 40 kidney disease-related proteins and 4 kidney damage-related proteins were achieved from urine of patients with kidney disease. These proteins need to be further determined.