An integrated analysis of lncRNAs and mRNAs expression profiles in the kidney of mice with lupus nephritis

Long non-coding RNAs (lncRNAs) are pervasively expressed and have been reported as potential biomarkers and therapeutic targets in various diseases, including systemic lupus erythematosus (SLE). However, there was limited information about lncRNAs expression in kidney tissue with lupus nephritis (LN), a serious complication of SLE. To explore the underlying molecular and cellular mechanisms of lncRNAs during pathogenesis of LN, RNA sequencing (RNA_seq) was performed to determine the lncRNAs and mRNAs expression of kidney tissues from LN (MRL/lpr) and control mouse. We identified 12, 979 novel lncRNAs in mouse. The expression profiles of both mRNA and lncRNA were significant different between LN and control mouse. In particular, both upregulated lncRNAs and mRNAs were more than downregulated ones in kidney tissue of LN mouse. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response associated pathway. KEGG analysis showed that both downregulated and upregulated genes were enriched in pathway including SLE pathway, about half of these SLE-assocaited genes were inflammatory factors. Moreover, we found that 2, 181 DElncRNAs potential targeted and regulated expresison of 778 mRNA in kidney tissues of LN. The results showed that 11 DE-LncRNAs targeted and co-expressed with six immune and SLE-assocaited genes. qPCR confirmed that lncRNA Gm20513 would positively regualte the expression of SLE-associated gene H2-Aa. In conclusion, our study demonstrates that lncRNA will influence the progression of LN and will provide some cues for further study of lncRNAs in LN. LncRNA-mRNA regulation network may have important value in LN diagnosis and therapy. RNA sequencing (RNA_seq) was performed to determine the lncRNAs and mRNAs expression of kidney tissues from LN (MRL/lpr) and control mouse长链非编码RNA（long non-coding RNAs, lncRNAs）广泛表达，且已被报道可作为包括系统性红斑狼疮（systemic lupus erythematosus, SLE）在内的多种疾病的潜在生物标志物与治疗靶点。然而，针对狼疮性肾炎（lupus nephritis, LN，SLE的严重并发症）患者肾组织中lncRNAs的表达情况，目前相关信息仍较为有限。为探究lncRNAs在狼疮性肾炎发病过程中的潜在分子与细胞机制，本研究采用RNA测序（RNA sequencing, RNA_seq）技术，对狼疮性肾炎模型小鼠（MRL/lpr）与正常对照小鼠的肾组织中lncRNAs及mRNA的表达水平进行检测。本研究在小鼠体内共鉴定出12979条新型lncRNAs。狼疮性肾炎小鼠与对照小鼠的mRNA及lncRNA表达谱均存在显著差异。具体而言，狼疮性肾炎小鼠肾组织中上调的lncRNAs与mRNA的数量均多于下调者。然而，基因本体（Gene Ontology, GO）富集分析显示，下调基因更多富集于免疫与炎症反应相关通路。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析结果表明，上调与下调基因均富集于包括SLE相关通路在内的多条通路，其中约半数与SLE相关的基因为炎症因子。此外，本研究发现2181个差异表达lncRNAs（differentially expressed lncRNAs, DElncRNAs）可潜在靶向调控狼疮性肾炎小鼠肾组织中778个mRNA的表达。分析结果显示，11个差异表达lncRNAs可与6个免疫相关及SLE相关基因形成靶向共表达关系。定量聚合酶链反应（quantitative polymerase chain reaction, qPCR）验证结果表明，lncRNA Gm20513可正向调控SLE相关基因H2-Aa的表达。综上，本研究证实lncRNAs可影响狼疮性肾炎的疾病进程，可为后续lncRNAs在狼疮性肾炎中的研究提供参考方向；lncRNA-mRNA调控网络在狼疮性肾炎的诊断与治疗中或具有重要应用价值。本研究采用RNA测序（RNA sequencing, RNA_seq）技术，对狼疮性肾炎模型小鼠（MRL/lpr）与正常对照小鼠的肾组织中lncRNAs及mRNA的表达水平进行检测。