炎症性肠病与IgA肾病共病特征基因及信号通路激活模式的整合分析

doi:10. 20223 / j. cnki. 1000-8535. 2026. 01. 007

摘要/Abstract

摘要： 目的免疫球蛋白A肾病（IgAN）与炎症性肠病（IBD）的相互作用机制尚未阐明。本研究旨在解析IBD与IgAN共病的关键特征基因及核心信号通路,以揭示肠–肾轴的分子调控网络。方法于GEO数据库获取IBD（GSE75214）和IgAN（GSE93798）基因表达谱,筛选差异表达基因（DEGs）。通过蛋白互作网络（PPI）和拓扑算法（MCC、MNC、Degree、EPC等）识别核心特征基因,并结合公共数据库（CTD、DISEASES和GeneCards）和单细胞转录组测序（GSE171314）进行验证。通过Nephroseq数据库验证基因表达与临床表型的相关性。结果共筛选出17个IBD-IgAN共病DEGs,PPI网络分析等确定以FOS、EGR1、CXCL2和JUNB为核心特征基因。功能富集分析显示白细胞介素-17（IL-17）信号通路显著激活。单细胞测序验证FOS、EGR1、CXCL2和JUNB基因在IgAN特异性高表达,并通过Nephroseq数据库验证其与尿蛋白和估算的肾小球滤过率下降（eGFR）显著相关。结论本研究揭示IBD与IgAN共享IL-17通路异常激活及FOS、EGR1、CXCL2和JUNB的基因网络,为开发基于肠–肾轴调控的靶向治疗策略提供理论依据。

关键词: IgA肾病, 炎症性肠病, 肠-肾轴, IL-17信号通路, 枢纽基因

Abstract: Objective The complex interplay between immunoglobulin A nephropathy（IgAN）and inflammatory bowel disease（IBD）remains poorly understood.This study aimed to identify key cross-talk genes and pivotal signaling pathways shared between IBD and IgAN,thereby elucidating the molecular regulatory network underlying the gut-kidney axis. Methods Transcriptomic datasets for IBD（GSE75214）and IgAN（GSE93798）were retrieved from the GEO database.Differentially expressed genes（DEGs）were screened,and shared DEGs were intersected.Protein-protein interaction（PPI）networks were constructed using STRING and Cytoscape,with topological algorithms applied to identify hub genes.Gene expression profiles were validated through（CTD,DISEASES and GeneCards）and single-cell RNA sequencing（GSE171314）and the Nephroseq database,focusing on clinical correlations with proteinuria and estimated glomerular filtration rate（eGFR）. Results Seventeen shared DEGs were identified between IBD and IgAN.PPI network analysis revealed FOS,EGR1,CXCL2 and JUNB as core hub genes.Functional enrichment analysis demonstrated significant activation of the interleukin-17（IL-17） signaling pathway.Single-cell sequencing confirmed the specific upregulation of these genes in renal tubular epithelial cells of IgAN patients,which was further validated to correlate with proteinuria and eGFR decline. Conclusions IBD and IgAN share aberrant activation of the IL-17 pathway and a co-regulatory gene network involving FOS,EGR1,CXCL2 and JUNB,providing a theoretical foundation for developing therapeutic strategies centered on the gut-kidney axis.

Key words: IgA nephropathy, inflammatory bowel disease, gut-kidney axis, IL-17 signaling pathway, hub genes

连兴基, 彭晓辉, 王衍慧, 杨媚, 刘丽兰, 黄玉宇. 炎症性肠病与IgA肾病共病特征基因及信号通路激活模式的整合分析[J]. 广州医药, 2026, 57(1): 46-55.

LIAN Xingji, PENG Xiaohui, WANG Yanhui, YANG Mei, LIU Lilan, HUANG Yuyu. Integrated analysis of shared signature genes and signaling pathway activation patterns between inflammatory bowel disease and IgA nephropathy[J]. Guangzhou Medical Journal, 2026, 57(1): 46-55.

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