Zheng Wen Jia, Liu Tao, Zhu Xiao Li, Zhang Yu Ting, Wei Liang Bing, Gao Ya Chen, Zhuang Xing Xing, Gao Jia Rong
Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China.
College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230011, Anhui, China.
Genes Genomics. 2025 Aug 18. doi: 10.1007/s13258-025-01670-7.
Immunoglobulin A nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis. Long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of various diseases, including kidney disorders. However, the involvement of lncRNAs in IgAN remains underexplored. This study aims to investigate the potential role of lncRNAs in IgAN by constructing a comprehensive lncRNA-miRNA-mRNA regulatory network.
An IgAN mouse model was established for the study. The expression profiles of lncRNAs and mRNAs were obtained via RNA sequencing (RNA-seq) to identify differentially expressed mRNAs and lncRNAs. A lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network was subsequently constructed through bioinformatics analysis, and pathway enrichment was explored through functional analyses. Validation of lncRNAs, miRNAs, and mRNAs was performed via Real-time quantitative polymerase chain reaction (RT-qPCR).
Histological analysis using hematoxylin and eosin (HE) staining and immunofluorescence confirmed the successful development of the IgAN mouse model. Enzyme-linked immunosorbent assay (ELISA) and biochemical index testing indicated significant increases in renal function markers, including Immunoglobulin A (IgA), Blood Urea Nitrogen (BUN), and Creatinine (CRE). RNA-seq analysis revealed 388 differentially expressed lncRNAs and 256 differentially expressed mRNAs. A bioinformatics-based ceRNA network, focused on inflammation and immune response, was successfully constructed, comprising 19 lncRNAs, 7 mRNAs, and 5 miRNAs. Functional enrichment analysis identified significant involvement of these lncRNAs in the MAPK, Ras, and PI3K-Akt signaling pathways. Finally, the RT-qPCR validation data agreed with the RNA-seq.
This study identified a novel lncRNA/miRNA/mRNA regulatory network involved in the pathogenesis of IgAN.
免疫球蛋白A肾病（IgAN）是原发性肾小球肾炎最常见的形式。长链非编码RNA（lncRNA）在包括肾脏疾病在内的各种疾病的发生和发展中起关键作用。然而，lncRNA在IgAN中的作用仍未得到充分研究。本研究旨在通过构建一个全面的lncRNA- miRNA- mRNA调控网络来探讨lncRNA在IgAN中的潜在作用。
建立IgAN小鼠模型用于本研究。通过RNA测序（RNA-seq）获得lncRNA和mRNA的表达谱，以鉴定差异表达的mRNA和lncRNA。随后通过生物信息学分析构建lncRNA介导的竞争性内源性RNA（ceRNA）调控网络，并通过功能分析探索通路富集。通过实时定量聚合酶链反应（RT-qPCR）对lncRNA、miRNA和mRNA进行验证。
苏木精和伊红（HE）染色及免疫荧光的组织学分析证实了IgAN小鼠模型的成功建立。酶联免疫吸附测定（ELISA）和生化指标检测表明，包括免疫球蛋白A（IgA）、血尿素氮（BUN）和肌酐（CRE）在内的肾功能指标显著升高。RNA-seq分析揭示了388个差异表达的lncRNA和256个差异表达的mRNA。成功构建了一个基于生物信息学的ceRNA网络，该网络聚焦于炎症和免疫反应，由19个lncRNA、7个mRNA和5个miRNA组成。功能富集分析确定这些lncRNA在丝裂原活化蛋白激酶（MAPK）、Ras和磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-Akt）信号通路中显著参与。最后，RT-qPCR验证数据与RNA-seq结果一致。
本研究确定了一个参与IgAN发病机制的新型lncRNA/miRNA/mRNA调控网络。
