Department of Nephrology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150086, People's Republic of China.
College of Bioinformatics Science and Technology, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150081, Heilongjiang Province, China.
BMC Nephrol. 2021 Nov 25;22(1):392. doi: 10.1186/s12882-021-02606-5.
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration.
The expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein-protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells.
Four downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration.
A potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients.
IgA 肾病（IgAN）是全球最常见的原发性肾小球肾炎，其诊断主要依赖于肾活检。然而，目前针对 IgAN 尚无特异性治疗方法。此外，其病因和潜在的分子事件仍需进一步探索。
从基因表达综合数据库（GEO）中下载 GSE64306 和 GSE93798 数据集，分别用于鉴定差异表达的 microRNA 和基因。利用 StarBase 和 TransmiR 数据库预测差异表达 microRNA（DE-miRNA）的靶基因和转录因子。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析以预测生物功能。构建 miRNA-mRNA 调控网络的综合分析，并鉴定蛋白质-蛋白质相互作用（PPI）网络和枢纽基因。利用 CIBERSORT 分析 IgAN 中的免疫细胞，并对枢纽基因与浸润免疫细胞进行相关性分析。
鉴定出 4 个下调的 microRNA 和 16 个上调的 microRNA。上调和下调的 DE-miRNA 分别有 45 个和 12 个靶基因。CDKN1A、CDC23、EGR1、HIF1A 和 TRIM28 是连接度最高的枢纽基因。CIBERSORT 显示 IgAN 中激活的自然杀伤细胞、M1 和 M2 巨噬细胞、CD4 幼稚 T 细胞和调节性 T 细胞数量增加。此外，IgAN 患者的 HIF1A、CDC23、TRIM28 和 CDKN1A 与免疫细胞浸润相关。
成功建立了一个潜在的与 IgAN 发病和进展相关的 miRNA-mRNA 调控网络。本研究结果可能通过靶向已建立的 miRNA-mRNA 相互作用网络来促进 IgAN 的诊断和治疗。浸润免疫细胞可能在 IgAN 发病机制中发挥重要作用。对这些免疫细胞的进一步研究可能有助于指导 IgAN 患者的免疫治疗。
