Cao Hualin, Tao Yuandong, Jin Ruyue, Li Pin, Zhou Huixia, Cheng Jiwen
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.
Ren Fail. 2025 Dec;47(1):2443032. doi: 10.1080/0886022X.2024.2443032. Epub 2025 Jan 1.
Obstructive nephropathy is one of the leading causes of kidney injury in infants and children. Increasing evidence has shown that transcription-related factors (TRFs), including transcription factors and cofactors, are associated with kidney diseases. However, a global landscape of dysregulated TRFs in pediatric patients with obstructive nephropathy is lacking.
We mined the data from our previous proteomic study for the TRF profile in pediatric patients with obstructive nephropathy and unilateral ureteral obstruction (UUO) mice. Gene ontology (GO) analysis was performed to determine pathways that were enriched in the dysregulated TRFs. We then took advantage of kidney samples from patients and UUO mice to verify the selected TRFs by immunoblots.
The proteomes identified a total of 140 human TRFs with 28 upregulated and 1 downregulated, and 160 murine TRFs with 88 upregulated and 1 downregulated (fold change >2 or <0.5). These dysregulated TRFs were enriched in the inflammatory signalings, such as janus kinase/signal transducer and activator of transcription (JAK-STAT) and tumor necrosis factor (TNF) pathways. Of note, the transforming growth factor (TGF)-β signaling pathway, which is the master regulator of organ fibrosis, was enriched in both patients and mice. Cross-species analysis showed 16 key TRFs that might mediate obstructive nephropathy in patients and UUO mice. Moreover, we verified a significant dysregulation of three previously unexplored TRFs; prohibitin (PHB), regulatory factor X 1 (RFX1), and activity-dependent neuroprotector homeobox protein (ADNP), in patients and mice.
Our study uncovered key TRFs in the obstructed kidneys and provided additional molecular insights into obstructive nephropathy.
梗阻性肾病是婴幼儿和儿童肾损伤的主要原因之一。越来越多的证据表明，转录相关因子（TRFs），包括转录因子和辅助因子，与肾脏疾病有关。然而，目前缺乏关于小儿梗阻性肾病患者中TRFs失调的整体情况。
我们从之前的蛋白质组学研究中挖掘小儿梗阻性肾病患者和单侧输尿管梗阻（UUO）小鼠的TRF谱数据。进行基因本体（GO）分析以确定在失调的TRFs中富集的通路。然后，我们利用患者和UUO小鼠的肾脏样本通过免疫印迹验证所选的TRFs。
蛋白质组共鉴定出140种人类TRFs，其中28种上调，1种下调；160种小鼠TRFs，其中88种上调，1种下调（倍数变化>2或<0.5）。这些失调的TRFs在炎症信号通路中富集，如Janus激酶/信号转导子和转录激活子（JAK-STAT）以及肿瘤坏死因子（TNF）通路。值得注意的是，作为器官纤维化主要调节因子的转化生长因子（TGF）-β信号通路在患者和小鼠中均有富集。跨物种分析显示有16个关键TRFs可能介导患者和UUO小鼠的梗阻性肾病。此外，我们验证了三种之前未被探索的TRFs；抑制素（PHB）、调节因子X1（RFX1）和活性依赖的神经保护同源框蛋白（ADNP）在患者和小鼠中存在显著失调。
我们的研究发现了梗阻肾脏中的关键TRFs，并为梗阻性肾病提供了更多的分子见解。
