LNCRNA Illumina sequencing results associated with renal fibrosis disease progression

Objective: To screen and identify long noncoding RNAs (lncRNAs) involved in the progression of renal fibrosis and to explore their functions. Methods: We used unilateral ureteral obstruction (UUO) to establish a rat model of renal fibrosis. The animals were randomly divided into four groups: control, model group at 2 weeks (MOD-2), MOD-4, and MOD-6. Renal function was monitored by measuring the levels of conventional biochemical biomarkers. Differentially expressed lncRNAs (DE-lncRNAs) between the control and model groups were screened, and their functions were annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene interaction networks were visualized using Cytoscape.

Results: Transcriptomic analysis revealed 243 DE-lncRNAs (82 upregulated, 161 downregulated) in the MOD-2 group compared with the control group, 216 DE-lncRNAs (95 upregulated, 121 downregulated) in the MOD-4 group, and 70 DE-lncRNAs (39 upregulated, 31 downregulated) in the MOD-6 group. Compared with the control group, the model groups were enriched in target genes involved in extracellular matrix–receptor interaction, arginine and proline metabolism, arachidonic acid metabolism, glutathione metabolism, peroxisome proliferator-activated receptor signaling, Janus kinase–signal transducer and activator of transcription signaling, phosphoinositide-3-kinase–Akt signaling, and calcium signaling. 

Conclusion: We speculate that the six upregulated DE-lncRNAs in the model groups may be involved in the occurrence and development of renal fibrosis, while the seven downregulated DE-lncRNAs may have inhibitory effects

研究目的：筛选并鉴定参与肾纤维化进程的长链非编码RNA（long noncoding RNAs，lncRNAs），并探究其功能。
研究方法：采用单侧输尿管梗阻（unilateral ureteral obstruction, UUO）构建大鼠肾纤维化模型，将实验动物随机分为四组：对照组、造模2周组（MOD-2）、造模4周组（MOD-4）及造模6周组（MOD-6）。通过检测常规生化生物标志物水平监测肾功能。筛选对照组与模型组间的差异表达长链非编码RNA（differentially expressed lncRNAs, DE-lncRNAs），并采用基因本体（Gene Ontology, GO）分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）分析对其功能进行注释。使用Cytoscape可视化基因互作网络。
研究结果：转录组分析显示，与对照组相比，MOD-2组存在243个差异表达长链非编码RNA（上调82个，下调161个），MOD-4组存在216个（上调95个，下调121个），MOD-6组存在70个（上调39个，下调31个）。与对照组相比，各模型组的靶基因显著富集于细胞外基质-受体相互作用、精氨酸与脯氨酸代谢、花生四烯酸代谢、谷胱甘肽代谢、过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor, PPAR）信号通路、贾纳斯激酶-信号转导与转录激活因子（Janus kinase–signal transducer and activator of transcription, JAK-STAT）信号通路、磷脂酰肌醇3-激酶-Akt（phosphoinositide-3-kinase-Akt, PI3K-Akt）信号通路以及钙信号通路。
研究结论：我们推测，模型组中6个上调的差异表达长链非编码RNA可能参与肾纤维化的发生与发展，而7个下调的差异表达长链非编码RNA可能发挥抑制作用。