Department 2 of Nephrology, Beijing Key Laboratory for Chronic Renal Disease and Blood Purification, Beijing Children's Hospital Affiliated to Capital Medical University, Key Laboratory of Major Diseases in Children, National Center for Children's Health, China, Beijing, 100045, China.
BMC Med Genomics. 2023 Nov 28;16(1):304. doi: 10.1186/s12920-023-01718-1.
In children with CKD, Protein Energy Wasting (PEW) is common, which affects the outcome of children and is an important cause of poor prognosis. We are aiming to explore the pathogenesis of muscle wasting in CKD-PEW children.
Blood samples of 32 children diagnosed with chronic kidney disease (CKD) and protein energy wasting (PEW) in our hospital from January 2016 to June 2021 were collected. RNA sequencing and bioinformatics analysis were performed.
Based on GO (Gene Ontology) functional enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and differential gene expression analysis, a total of 25 CKD-PEW related genes were obtained including CRP, IL6, TNF, IL1B, CXCL8, IL12B, IL12A, IL18, IL1A, IL4, IL10, TGFB2, TGFB1, TGFB3, ADIPOQ, NAMPT, RETN, RETNLB, LEP, CD163, ICAM1, VCAM1, SELE, NF-κB1, NF-κB2. The most significantly differentially expressed gene was NF-κB2 (adjusted P = 2.81 × 10), and its expression was up-regulated by 3.92 times (corresponding log2FoldChange value was 1.979). Followed by RETN (adjusted P = 1.63 × 10), and its expression was up-regulated by 8.306 times (corresponding log2FoldChange value was 2.882). SELE gene were secondly significant (adjusted P = 5.81 × 10), and its expression was down-regulated by 22.05 times (corresponding log2FoldChange value was -4.696).
A variety of inflammatory factors are involved in the pathogenesis of CKD-PEW in children, and chronic inflammation may lead to the development of muscle atrophy in CKD-PEW. It is suggested for the first time that NF-κB is a key gene in the pathogenesis of muscle wasting in CKD-PEW children, and its increased expression may play an important role in the pathogenesis of muscle wasting in children with CKD-PEW.
在患有 CKD 的儿童中，蛋白能量消耗（PEW）很常见，这会影响儿童的预后，是预后不良的重要原因。我们旨在探索 CKD-PEW 儿童肌肉萎缩的发病机制。
收集我院 2016 年 1 月至 2021 年 6 月诊断为慢性肾脏病（CKD）和蛋白能量消耗（PEW）的 32 例儿童的血样。进行 RNA 测序和生物信息学分析。
基于 GO（基因本体论）功能富集分析、KEGG（京都基因与基因组百科全书）通路富集分析和差异基因表达分析，共获得 25 个与 CKD-PEW 相关的基因，包括 CRP、IL6、TNF、IL1B、CXCL8、IL12B、IL12A、IL18、IL1A、IL4、IL10、TGFB2、TGFB1、TGFB3、ADIPOQ、NAMPT、RETN、RETNLB、LEP、CD163、ICAM1、VCAM1、SELE、NF-κB1、NF-κB2。最显著差异表达的基因是 NF-κB2（调整后的 P=2.81×10），其表达上调 3.92 倍（相应的 log2FoldChange 值为 1.979）。其次是 RETN（调整后的 P=1.63×10），其表达上调 8.306 倍（相应的 log2FoldChange 值为 2.882）。SELE 基因也很显著（调整后的 P=5.81×10），其表达下调 22.05 倍（相应的 log2FoldChange 值为-4.696）。
多种炎症因子参与儿童 CKD-PEW 的发病机制，慢性炎症可能导致 CKD-PEW 肌肉萎缩的发展。首次提出 NF-κB 是 CKD-PEW 儿童肌肉萎缩发病机制中的关键基因，其表达增加可能在 CKD-PEW 儿童肌肉萎缩发病机制中发挥重要作用。
