Liu Yanli, Guo Runsheng, Hao Guojun, Xiao Jun, Bao Yi, Zhou Jing, Chen Qinkai, Wei Xin
Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of osteology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Gene. 2015 Jun 15;564(2):210-9. doi: 10.1016/j.gene.2015.03.050. Epub 2015 Mar 28.
Increasing amounts of evidence have indicated that noncoding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contributions of ncRNAs, especially long noncoding RNAs (lncRNAs), to peritoneal fibrosis remain largely unknown. The aim of this study was to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of peritoneal fibrosis. Microarray expression profiles of the miRNAs, lncRNAs and mRNAs were determined in normal control peritoneum and in a mouse model of peritoneal dialysis fluid (PDF)-induced fibrotic peritoneum. Differential expression, pathway and gene network analyses were developed to identify possible functional RNA molecules in peritoneal fibrosis. Compared to the normal control, 232 lncRNAs (127 up-regulated and 105 down-regulated), 154 mRNAs (87 up-regulated and 67 down-regulated) and 15 miRNAs (14 miRNAs up-regulated and 1 down-regulated) were differentially expressed in the fibrotic peritoneum. Among the differentially expressed ncRNAs, 9 lncRNAs and 5 miRNAs were validated by real-time RT-PCR. Pathway analysis showed that the Jak-STAT, TGF-beta and MAPK signaling pathways had a close relationship with peritoneal fibrosis. Gene co-expression network analysis identified many genes, including JunB, HSP72, and Nedd9. It also identified lncRNAs AK089579, AK080622, and ENSMUST00000053838 and miRNAs miR-182 and miR-488. All of these species potentially play a key role in peritoneal fibrosis. Our results provide a foundation and an expansive view of the roles and mechanisms of ncRNAs in PDF-induced peritoneal fibrosis.
越来越多的证据表明,非编码RNA(ncRNAs)在各种生物学过程中具有重要的调控潜力。然而,ncRNAs,尤其是长链非编码RNA(lncRNAs)对腹膜纤维化的作用仍 largely未知。本研究的目的是调查miRNA、lncRNA和mRNA的表达谱及其在腹膜纤维化过程中的潜在作用。在正常对照腹膜和腹膜透析液(PDF)诱导的纤维化腹膜小鼠模型中测定了miRNA、lncRNA和mRNA的微阵列表达谱。开展了差异表达、通路和基因网络分析,以识别腹膜纤维化中可能的功能性RNA分子。与正常对照相比,在纤维化腹膜中有232个lncRNAs(127个上调和105个下调)、154个mRNA(87个上调和67个下调)和15个miRNAs(14个miRNAs上调和1个下调)差异表达。在差异表达的ncRNAs中,9个lncRNAs和5个miRNAs通过实时RT-PCR得到验证。通路分析表明,Jak-STAT、TGF-β和MAPK信号通路与腹膜纤维化密切相关。基因共表达网络分析鉴定出许多基因,包括JunB、HSP72和Nedd9。它还鉴定出lncRNAs AK089579、AK080622和ENSMUST00000053838以及miRNAs miR-182和miR-488。所有这些物种可能在腹膜纤维化中起关键作用。我们的结果为ncRNAs在PDF诱导的腹膜纤维化中的作用和机制提供了基础和广阔的视角。