Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324Jingwu Road, Jinan, China.
Department of Minimally Invasive Urology, Jinan Children's Hospital, Jinan, China.
BMC Nephrol. 2024 May 8;25(1):158. doi: 10.1186/s12882-024-03592-0.
Ureteropelvic junction obstruction (UPJO) is the most common cause of pediatric congenital hydronephrosis, and continuous kidney function monitoring plays a role in guiding the treatment of UPJO. In this study, we aimed to explore the differentially expressed proteins (DEPs) in the urinary extracellular vesicles(uEVs) of children with UPJO and determine potential biomarkers of uEVs proteins that reflect kidney function changes.
Preoperative urine samples from 6 unilateral UPJO patients were collected and divided into two groups: differential renal function (DRF) ≥ 40% and DRF < 40%.We subsequently used data-independent acquisition (DIA) to identify and quantify uEVs proteins in urine, screened for DEPs between the two groups, and analyzed biofunctional enrichment information. The proteomic data were evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA) in a new UPJO testing cohort.
After one-way ANOVA, a P adj value < 0.05 (P-value corrected by Benjamin-Hochberg) was taken, and the absolute value of the difference multiple was more than 1.5 as the screening basis for obtaining 334 DEPs. After analyzing the enrichment of the DEPs according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment combined with the protein-protein interaction (PPI) network results, we selected nicotinamide adenine dinucleotide-ubiquinone oxidoreductase core subunit S1 (NDUFS1) for further detection. The expression of NDUFS1 in uEVs was significantly lower in patients with DRF < 40% (1.182 ± 0.437 vs. 1.818 ± 0.489, P < 0.05), and the expression level of NDUFS1 was correlated with the DRF in the affected kidney (r = 0.78, P < 0.05). However, the NDUFS1 concentration in intravesical urine was not necessarily related to the change in DRF (r = 0.28, P = 0.24).
Reduced expression of NDUFS1 in uEVs might indicate the decline of DRF in children with UPJO.
肾盂输尿管连接部梗阻（UPJO）是小儿先天性肾积水最常见的原因，连续肾功能监测在指导 UPJO 的治疗中起着重要作用。本研究旨在探讨 UPJO 患儿尿细胞外囊泡（uEVs）中的差异表达蛋白（DEPs），并确定反映肾功能变化的 uEVs 蛋白的潜在生物标志物。
收集 6 例单侧 UPJO 患儿术前尿液标本，根据患侧分肾功能（DRF）是否≥40%分为两组：DRF≥40%和 DRF<40%。随后采用数据非依赖性采集（DIA）技术对尿液中 uEVs 蛋白进行鉴定和定量，筛选两组间的 DEPs，并分析生物功能富集信息。在新的 UPJO 检测队列中，通过 Western 印迹和酶联免疫吸附试验（ELISA）对蛋白质组学数据进行评估。
经单因素方差分析（one-way ANOVA），取 P 值校正后（经 Benjamin-Hochberg 校正）<0.05，差异倍数的绝对值>1.5 作为筛选获得 334 个 DEPs 的依据。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，联合蛋白-蛋白相互作用（PPI）网络结果，对 DEPs 进行富集分析，选择 NADH 泛醌氧化还原酶核心亚基 S1（NDUFS1）进行进一步检测。结果显示，DRF<40%的患儿 uEVs 中 NDUFS1 的表达明显降低（1.182±0.437 比 1.818±0.489，P<0.05），且 NDUFS1 的表达水平与患侧肾 DRF 呈正相关（r=0.78，P<0.05）。然而，膀胱内尿液中的 NDUFS1 浓度不一定与 DRF 的变化相关（r=0.28，P=0.24）。
UPJO 患儿 uEVs 中 NDUFS1 表达降低可能提示 DRF 下降。
