LncRNA-AV310809在腹膜透析相关腹膜纤维化中的作用及机制研究

项目名称： LncRNA-AV310809在腹膜透析相关腹膜纤维化中的作用及机制研究

项目编号： No.81500586

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 魏昕

作者单位： 南昌大学

项目金额： 18万元

中文摘要： 腹膜纤维化是影响腹膜透析效果，导致患者退出腹透最主要的原因，目前，其发生及调控机制尚不明确，仍无有效的解决办法。在前期研究中，我们构建腹膜透析相关腹膜纤维化动物模型，并通过基因芯片进行了腹膜纤维化差异lncRNA的筛选，发现lncRNA-AV310809在纤维化的腹膜组中显著高表达，而上调AV310809的表达可促进腹膜间皮细胞EMT的发生及细胞外基质的合成。通过Pathway、Network分析，我们进一步发现AV310809与纤维化相关信号通路-Wnt通路中的重要基因Wnt2和Wnt5的表达呈高度正相关。因此，我们推测AV310809可能参与了腹膜纤维化的发生及调控。基于以上前期工作，本课题拟从动物，细胞及分子水平验证AV310809表达与腹膜纤维化的关系，并明确其对Wnt信号通路的调控作用，从而揭示腹膜透析相关腹膜纤维化发生的新机制，为临床腹膜纤维化的治疗提供新的潜在药物治疗靶点。

中文关键词： 腹膜透析；腹膜纤维化；长链非编码RNA；Wnt；信号通路

英文摘要： Peritoneal fibrosis is a common complication of long-term peritoneal dialysis, and contributes to encapsulating peritoneal sclerosis and eventually peritoneal ultrafiltration failure, which restricts the wide application of peritoneal dialysis. The prevention and treatment of peritoneal fibrosis is important to prolong peritoneal dialysis treatment. However, the mechanism of the peritoneal fibrosis is not well understood. Long noncoding RNAs (lncRNAs) are defined as RNA molecules over 200nt in length which do not encode for a protein. Recent studies indicated that lncRNAs play a critical role in regulation of diverse physiological and pathological processes. Our preliminary studies showed that there were systematic differences in the expression of lncRNAs and protein-coding RNAs between fibrosis peritoneal and normal tissue. Futhermore, the expression of lncRNA AV310809 was significantly lower (more than 5 fold) in fibrotic peritoneal, and over-expression of AV310809 can significantly promote the epithelial-mesenchymal transition (EMT) process and the synthesis of ECM proteins induced by TGF-β1. Furthermore, By Pathway and Network analysis, we found the expression of AV310809 was highly correlated with Wnt2 and Wnt5 (pearson’s correlation coefficients≧0.98), which played the key role in the Wnt signal pathway. These results indicated that lncRNA AV310809 may participates in the process of peritoneal fibrosis. Therefore, our study is to investigate the function and the regulation mechanism of lncRNA AV310809 in the process of peritoneal dialysis associtated peritoneal fibrosis by using biological informatics, real-time PCR, RIP, gene cloning and RNA interference methods in vitro/vivo researches.

英文关键词： peritoneal dialysis;peritoneal fibrosis;long noncodig RNA;Wnt signal pathway