Wang Juan, Wu Xiongfei, Tu Yafang, Dang Jianzhong, Cai Zhitao, Liao Wenjing, Quan Weili, Wei Yaxun
Nephrology Department, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
ABLife BioBigData Institute, Wuhan, Hubei, China.
PeerJ. 2021 Feb 16;9:e10668. doi: 10.7717/peerj.10668. eCollection 2021.
Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identified 12,979 novel lncRNAs in mouse. The expression profiles of both mRNAs and lncRNAs were differed significantly between LN and control mice. In particular, there were more upregulated lncRNAs and mRNAs than downregulated ones in the kidney tissues of LN mice. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response-associated pathways. KEGG analysis showed that both downregulated and upregulated genes were enriched in a number of pathways, including the SLE pathway, and approximately half of these SLE-associated genes encoded inflammatory factors. Moreover, we observed that 2,181 DElncRNAs may have targeted and regulated the expression of 778 mRNAs in LN kidney tissues. The results of this study showed that 11 DElncRNAs targeted and were co-expressed with six immune and SLE-associated genes. qPCR analysis confirmed that lncRNA Gm20513 positively regulated the expression of the SLE-associated gene H2-Aa. In conclusion, the results of our study demonstrates that lncRNAs influence the progression of LN and provide some cues for further study of lncRNAs in LN. These results regarding the lncRNA-mRNAregulatory network may have important value in LN diagnosis and therapy.
长链非编码RNA(lncRNAs)持续表达,在多种疾病中被描述为潜在的生物标志物和治疗靶点。然而,关于lncRNA在狼疮性肾炎(LN)(系统性红斑狼疮(SLE)的一种严重并发症)肾脏组织中的表达信息有限。在本研究中,进行了RNA测序(RNA-seq)以表征LN(MRL/lpr)小鼠和对照小鼠肾脏组织中的lncRNA和mRNA表达。我们在小鼠中鉴定出12,979个新的lncRNAs。LN小鼠和对照小鼠之间的mRNA和lncRNA表达谱存在显著差异。特别是,LN小鼠肾脏组织中上调的lncRNAs和mRNAs比下调的更多。然而,基因本体(GO)分析表明,更多下调基因富集在免疫和炎症反应相关途径中。京都基因与基因组百科全书(KEGG)分析表明,下调和上调的基因都富集在许多途径中,包括SLE途径,并且这些与SLE相关的基因中约有一半编码炎症因子。此外,我们观察到2,181个差异表达lncRNAs(DElncRNAs)可能靶向并调节了LN肾脏组织中778个mRNAs的表达。本研究结果表明,11个DElncRNAs靶向6个免疫和SLE相关基因并与之共表达。定量聚合酶链反应(qPCR)分析证实lncRNA Gm20513正向调节SLE相关基因H2-Aa的表达。总之,我们的研究结果表明lncRNAs影响LN的进展,并为进一步研究LN中的lncRNAs提供了一些线索。这些关于lncRNA-mRNA调控网络的结果可能在LN的诊断和治疗中具有重要价值。