Department of Nephrology, 89657The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Institute of Chronic Kidney Disease, 89657Wenzhou Medical University, Wenzhou, China.
Lupus. 2021 Dec;30(14):2248-2255. doi: 10.1177/09612033211061482. Epub 2021 Dec 18.
Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN.
We herein employed high-throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.
Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway.
This study provides a novel insight for studying the mechanism of LN.
狼疮肾炎（LN）是系统性红斑狼疮（SLE）的主要靶器官并发症，其发病机制尚不完全清楚。越来越多的证据表明 tRNA 衍生的小 RNA（tsRNAs）在人类疾病中具有潜在的重要作用。本研究旨在探讨 tsRNAs 在 LN 中的潜在作用。
我们采用高通量测序筛选 LN 组和对照组肾组织中 tsRNAs 的表达谱。为了验证测序数据，我们进行了定量实时 PCR（qRT-PCR）分析。采用线性回归分析验证的 tsRNAs 表达与临床指标的相关性。还预测了潜在的靶基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析注释 tsRNAs 的生物学功能。
我们的研究结果表明，与对照组相比，LN 患者肾脏组织中 tsRNAs 的表达谱明显改变。总体而言，LN 组有 160 个 tsRNAs 表达显著失调，其中 79 个上调，81 个下调。随后的 qRT-PCR 结果证实了候选 tsRNAs 的差异表达。相关性分析结果发现，验证的 tsRNAs 的表达与临床指标相关。靶基因预测结果表明，验证的 tsRNAs 可能作用于 712 个靶基因。进一步的生物信息学分析表明，tsRNAs 可能通过几种相关途径参与 LN 的发病机制，包括细胞黏附分子、MAPK 信号通路、PI3K-Akt 信号通路和 B 细胞受体信号通路。
本研究为研究 LN 的发病机制提供了新的视角。
