Comprehensive analysis of aberrantly expressed profiles of mRNA and its relationship with serum galactose-deficient IgA1 level in IgA nephropathy
Comprehensive analysis of aberrantly expressed profiles of mRNA and its relationship with serum galactose-deficient IgA1 level in IgA nephropathy
复制标题
IgA肾病mRNA异常表达谱综合分析及其与血清半乳糖缺乏型IgA1水平的关系
DOI：
10.1186/s12967-019-2064-3
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发表时间：
2019-09-23
影响因子：
7.4
通讯作者：
Yan, Tiekun
中科院分区：
文献类型：
--
作者：
Liu, Youxia;Liu, Xiangchun;Yan, Tiekun
背景免疫球蛋白A肾病（ImmunoglobulinA nephropathy，IgAN）是终末期肾病的主要病因。先前的IgAN的mRNA微阵列分析研究揭示了不一致的数据。我们试图通过整合血细胞中IgAN基因表达数据集并进行系统的实验验证来识别异常表达的基因和生物学途径。我们还探讨了IgAN中靶基因与半乳糖缺陷型IgA 1（Gd-IgA 1）的关系。基因本体论（GO）富集和京都基因和基因组百科全书（KEGG）分析用于功能分析。对从B细胞分离的RNA进行深度测序用于微阵列验证。靶mRNA的表达和Gd-IgA 1水平在血清中的关系也studied.ResultsThree研究与微阵列表达谱数据集符合我们的纳入标准。我们在35例IgAN患者和19例健康对照的3个GEO数据集中鉴定了655个异常表达基因，包括319个上调基因和336个下调基因。根据GO期的生物学过程，这些基因主要与戊糖-磷酸分流、非氧化分支、胚后相机型眼发育和白细胞活化有关。芯片数据的KEGG通路分析显示，这些异常表达的基因在人类T细胞白血病病毒1感染、癌症中的蛋白多糖、用于伊加产生和自噬的肠道免疫网络中富集。我们进一步对从一组独立的5名IgAN患者和3名具有相同临床和人口统计学特征的健康人的B细胞中分离的mRNA进行深度测序。77个基因与上述655个差异表达基因重叠，其中上调基因43个，下调基因34个。我们接下来研究这些基因表达是否与IgAN患者中的Gd-IgA 1水平相关。结论IgAN患者肠道免疫网络中存在表达异常的基因，这些基因参与了伊加的产生和自噬过程，B细胞中的PTEN可能参与了Gd-IgA 1的产生机制。
BackgroundImmunoglobulin A nephropathy (IgAN) is the leading cause of end-stage kidney disease. Previous mRNA microarray profiling studies of IgAN revealed inconsistent data. We sought to identify the aberrantly expressed genes and biological pathways by integrating IgAN gene expression datasets in blood cells and performing systematically experimental validation. We also explored the relationship between target genes and galactose-deficient IgA1 (Gd-IgA1) in IgAN.MethodsWe retrieved Gene Expression Omnibus (GEO) datasets of IgAN. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional analysis. Deep sequencing on RNA isolated from B cells was used for microarray validation. The relationship between target mRNA expressions and Gd-IgA1 levels in serum were also studied.ResultsThree studies with microarray expression profiling datasets met our inclusion criteria. We identified 655 dyregulated genes, including 319 up-regulated and 336 down-regulated genes in three GEO datasets with a total of 35 patients of IgAN and 19 healthy controls. Based on biological process in GO term, these dyregulated genes are mainly related to pentose-phosphate shunt, non-oxidative branch, post-embryonic camera-type eye development and leukocyte activation. KEGG pathway analysis of microarray data revealed that these aberrantly expressed genes were enriched in human T-cell leukemia virus 1 infection, proteoglycans in cancer, intestinal immune network for IgA production and autophagy. We further performed deep sequencing on mRNAs isolated from B cells of an independent set of five patients with IgAN and three healthy persons with the same clinical and demographic characteristics. Seventy-seven genes overlapped with 655 differentially regulated genes mentioned above, including 43 up-regulated and thirty-four down-regulated genes. We next investigated whether these genes expression correlated with Gd-IgA1 levels in IgAN patients. Pearson correlation analyses showedPTEN(phosphatase and tensin homolog) was the most powerful gene negatively correlated with Gd-IgA1 levels.ConclusionsThese results demonstrated that dyregulated genes in patients with IgAN were enriched in intestinal immune network for IgA production and autophagy process, andPTENin B cells might be involved in the mechanism of Gd-IgA1 production.