新疆地区IgA肾病尿液差异蛋白质组学分析

Screening of urinary disease-related proteins in Xinjiang patients with IgA nephropathy based on proteomics data analysis

目的应用尿液差异蛋白质组学技术检测新疆维吾尔族与汉族IgA肾病(IgA nephropathy,IgAN)患者尿蛋白组学特征,为IgAN早期诊断寻找新的潜在生物标志物。方法采用质谱(SELDI-TOT-MS)iTRAQ绝对定量技术,对新疆地区维吾尔族、汉族IgAN患者(各12例)与健康对照组(各12例)的尿液样本进行分析,以了解IgAN病理生理过程影响、探索可能的发病机制及是否存在种族差异蛋白。结果健康对照组中汉族与维吾尔族种族尿液差异蛋白有37种,维吾尔族较汉族健康对照组明显上调的有19种,主要参与溶解和消化蛋白、花生四烯酸的代谢、补体途径代谢、甲状腺代谢、细胞因子受体应答、细胞间信号转导等生物学作用。IgAN疾病组共鉴定出276种蛋白,较健康对照组尿液差异蛋白59种,其中在维吾尔族、汉族IgAN组共有的尿液差异蛋白有32种,如:激肽释放酶(KLK3)、唾液酸蛋白(BSP)、丝氨酸抑制蛋白酶-1(SERPINC1)等,主要生物学功能有补体途径代谢、细胞凋亡、细胞外基质受体相互作用等。纤连蛋白(FGA)、硫氧还蛋白(TXN)、集聚蛋白(AGRN)、玻连蛋白(VTN)等参与凝血、组织纤维化等生物功能。IgAN疾病组维吾尔族较汉族尿液差异蛋白明显上调蛋白3种(FC≥1.5),主要集中在PI3K-Akt信号转导通路。结论维、汉种族间存在尿液差异蛋白,需进一步阐明其与发病机制、临床及病理表型间的联系。IgAN尿液差异蛋白需要在大样本组中进一步验证,但他们构成了IgAN初步生物标记候选标志物的基线数据。

Objective To explore kidney disease-related proteins and kidney damage-related proteins in urine of Uygur patients with IgA nephropathy. Methods Urine proteomic data of Uygur and Han patients with IgA nephropathy were collected.Urine proteomic data of healthy subjects were obtained from Healthy blood donors. Results The data from urine proteomic of Uygur patients with IgA nephropathy were compared with Han patients with IgA nephropathy.There were proteins which enriched in Uygur patients with IgA nephropathy 19 up-regulated types, which were involved in the metabolism of soluble and digestive proteins, the metabolism of four acids, complement pathway metabolism, thyroid metabolism, cytokine receptor response, and intercellular signaling.Compared with the healthy control group of urine 59 kinds of proteins, which were found in the urine of IgAN group and there were 32 kinds of common proteins, such as KLK3, BSP, SERPINC1. The main biological functions were complement pathway metabolism, cell apoptosis and extracellular matrix receptor interactions. IgAN Uygur group over the Han group was significantly up-regulated proteincompared with Han group, it was mainly concentrated in the PI3K-Akt signal transduction pathway. Conclusions By comparing data from above proteomic, SERPINC, Klk3, BSP may be used as candidate biomarkers for diagnosis of IgAN. FGA, TxN, AGRN and VTN can be used to judge the disease activity and clinical markers of pathological phenotype.These proteins need to be further determined.