Tripathy Anindita, Yedla Poornachandra, Vishnubhotla Ravikanth V, Sekaran Anuradha, Keithi Reddy Sai Ram
Department of Genetics and Bioinformatics, Asian Healthcare Foundation, Hyderabad, Telangana 500032, India.
Department of Nephrology, AIG (Mayo Clinic Care Network) Hospital, Hyderabad, Telangana 500032, India.
Biomed Rep. 2023 Apr 4;18(5):35. doi: 10.3892/br.2023.1617. eCollection 2023 May.
Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease with rapid development to end stage renal disease, requiring renal replacement therapy. Genome-wide studies suggest geographical variations in genetic susceptibility to IgAN and disease progression. Specific 'candidate genes' were indicated to correlate with different functions that are involved in the pathogenesis of renal conditions. MicroRNAs (miRNAs/miRs) have a major role in mRNA degradation or translation repression, thereby regulating the expression of their target proteins. Previously, a small number of miRNAs were reported to have direct associations with IgAN. In the present study, new miRNAs linked to IgAN were identified in the Indian population. The miRNA was isolated from kidney biopsies of patients with IgAN (n=6) and healthy control tissue from patients with renal cell carcinoma (n=6). The sequencing results indicated that the miRNA percentage acquired from controls and patients with IgAN was 5.61 and 4.35%, respectively. From the results, 10 upregulated and 15 downregulated miRNAs were identified. Of the 25 differentially expressed miRNAs (DEMs), miR-181a-5p, miR-28-3p, let-7g-5p, miR-92a-3p and miR-30c-5p were not reported previously. Furthermore, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the target genes of the DEMs were mainly enriched in pathways such as cancer, ErbB signalling, proteoglycans in cancer, Hippo signalling and MAPK pathways. The newly identified miRNAs may impact the behaviour of tissues or IgA deposition by regulating signalling pathways, which forms a basis for future studies aimed at improving the diagnosis and care of patients with IgAN in the Indian community.
免疫球蛋白A肾病（IgAN）是最常见的肾小球疾病，可迅速发展至终末期肾病，需要进行肾脏替代治疗。全基因组研究表明，IgAN的遗传易感性和疾病进展存在地理差异。特定的“候选基因”被指出与肾脏疾病发病机制中涉及的不同功能相关。微小RNA（miRNA/miR）在mRNA降解或翻译抑制中起主要作用，从而调节其靶蛋白的表达。此前，有少数miRNA被报道与IgAN直接相关。在本研究中，在印度人群中鉴定出与IgAN相关的新miRNA。从IgAN患者（n = 6）的肾活检组织和肾细胞癌患者的健康对照组织（n = 6）中分离出miRNA。测序结果表明，从对照组和IgAN患者中获得的miRNA百分比分别为5.61%和4.35%。根据结果，鉴定出10个上调的miRNA和15个下调的miRNA。在这25个差异表达的miRNA（DEM）中，miR-181a-5p、miR-28-3p、let-7g-5p、miR-92a-3p和miR-30c-5p此前未被报道。此外，京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析表明，DEM的靶基因主要富集在癌症、表皮生长因子受体（ErbB）信号通路、癌症中的蛋白聚糖、Hippo信号通路和丝裂原活化蛋白激酶（MAPK）信号通路等途径中。新鉴定的miRNA可能通过调节信号通路影响组织行为或IgA沉积，这为未来旨在改善印度社区IgAN患者诊断和护理的研究奠定了基础。
